Current therapeutic targets and multifaceted physiological impacts of caffeine

. 2023 Dec ; 37 (12) : 5558-5598. [epub] 20230907

Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid37679309

Grantová podpora
RVO Institute of Biotechnology of the Czech Academy of Sciences v.v.i., Institutional Research Concept
86652036 Institute of Biotechnology of the Czech Academy of Sciences v.v.i., Institutional Research Concept
2021R1C1C1006336 Basic Science Research Program, South Korea
2021M3A9G8022959 Bio & Medical Technology Development Program of the Ministry of Science, ICT (NRF), South Korea

Caffeine, which shares consubstantial structural similarity with purine adenosine, has been demonstrated as a nonselective adenosine receptor antagonist for eliciting most of the biological functions at physiologically relevant dosages. Accumulating evidence supports caffeine's beneficial effects against different disorders, such as total cardiovascular diseases and type 2 diabetes. Conversely, paradoxical effects are also linked to caffeine ingestion in humans including hypertension-hypotension and tachycardia-bradycardia. These observations suggest the association of caffeine action with its ingested concentration and/or concurrent interaction with preferential molecular targets to direct explicit events in the human body. Thus, a coherent analysis of the functional targets of caffeine, relevant to normal physiology, and disease pathophysiology, is required to understand the pharmacology of caffeine. This review provides a broad overview of the experimentally validated targets of caffeine, particularly those of therapeutic interest, and the impacts of caffeine on organ-specific physiology and pathophysiology. Overall, the available empirical and epidemiological evidence supports the dose-dependent functional activities of caffeine and advocates for further studies to get insights into the caffeine-induced changes under specific conditions, such as asthma, DNA repair, and cancer, in view of its therapeutic applications.

Zobrazit více v PubMed

Abbasi, A., Kukia, N. R., Froushani, S. M. A., & Hashemi, S. M. (2018). Nicotine and caffeine alter the effects of the LPS- primed mesenchymal stem cells on the co-cultured neutrophils. Life Sciences, 199, 41-47. https://doi.org/10.1016/j.lfs.2018.03.009

Abbott, N. J., Patabendige, A. A., Dolman, D. E., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood-brain barrier. Neurobiology of Disease, 37(1), 13-25. https://doi.org/10.1016/j.nbd.2009.07.030

Abdel-Hady, H., Nasef, N., Shabaan, A. E., & Nour, I. (2015). Caffeine therapy in preterm infants. World Journal of Clinical Pediatrics, 4(4), 81-93. https://doi.org/10.5409/wjcp.v4.i4.81

Abo-Salem, O. M., Hayallah, A. M., Bilkei-Gorzo, A., Filipek, B., Zimmer, A., & Müller, C. E. (2004). Antinociceptive effects of novel A2B adenosine receptor antagonists. Journal of Pharmacology and Experimental Therapeutics, 308(1), 358-366.

Abramson, V. G., Supko, J. G., Ballinger, T., Cleary, J. M., Hilton, J. F., Tolaney, S. M., Chau, N. G., Cho, D. C., Pearlberg, J., Lager, J., Shapiro, G. I., & Arteaga, C. L. (2017). Phase Ib study of safety and pharmacokinetics of the PI3K inhibitor SAR245408 with the HER3-neutralizing human antibody SAR256212 in patients with solid Tumors. Clinical Cancer Research, 23(14), 3520-3528. https://doi.org/10.1158/1078-0432.CCR-16-1764

Acheson, K. J., Gremaud, G., Meirim, I., Montigon, F., Krebs, Y., Fay, L. B., Gay, L. J., Schneiter, P., Schindler, C., & Tappy, L. (2004). Metabolic effects of caffeine in humans: Lipid oxidation or futile cycling? The American Journal of Clinical Nutrition, 79(1), 40-46. https://doi.org/10.1093/ajcn/79.1.40

Addicott, M. A. (2014). Caffeine use disorder: A review of the evidence and future implications. Current Addiction Reports, 1(3), 186-192.

Addicott, M. A., Yang, L. L., Peiffer, A. M., Burnett, L. R., Burdette, J. H., Chen, M. Y., Hayasaka, S., Kraft, R. A., Maldjian, J. A., & Laurienti, P. J. (2009). The effect of daily caffeine use on cerebral blood flow: How much caffeine can we tolerate? Human Brain Mapping, 30(10), 3102-3114. https://doi.org/10.1002/hbm.20732

Aden, U., Halldner, L., Lagercrantz, H., Dalmau, I., Ledent, C., & Fredholm, B. B. (2003). Aggravated brain damage after hypoxic ischemia in immature adenosine A2A knockout mice. Stroke, 34(3), 739-744. https://doi.org/10.1161/01.STR.0000060204.67672.8B

Akinleye, A., Avvaru, P., Furqan, M., Song, Y. P., & Liu, D. L. (2013). Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics. Journal of Hematology & Oncology, 6, 88. https://doi.org/10.1186/1756-8722-6-88

Al Reef, T., & Ghanem, E. (2018). Caffeine: Well-known as psychotropic substance, but little as immunomodulator. Immunobiology, 223(12), 818-825. https://doi.org/10.1016/j.imbio.2018.08.011

Alasmari, F. (2020). Caffeine induces neurobehavioral effects through modulating neurotransmitters. Saudi Pharmaceutical Journal, 28(4), 445-451. https://doi.org/10.1016/j.jsps.2020.02.005

Alsabri, S. G., Mari, W. O., Younes, S., Elsadawi, M. A., & Oroszi, T. L. (2021). Kinetic and dynamic description of caffeine (vol 8, pg 3, 2018). Journal of Caffeine and Adenosine Research, 11(4), 107. https://doi.org/10.1089/caff.2017.0011.correx

Aluko, R. E. (2021). Food-derived Acetylcholinesterase inhibitors as potential agents against Alzheimer's disease. eFood, 2(2), 49-58.

Amchin, J., Zarycranski, W., Taylor, K. P., Albano, D., & Klockowski, P. M. (1999). Effect of venlafaxine on CYP1A2-dependent pharmacokinetics and metabolism of caffeine. Journal of Clinical Pharmacology, 39(3), 252-259.

Anderson, C. W. (1993). DNA damage and the DNA-activated protein kinase. Trends in Biochemical Sciences, 18(11), 433-437.

Andrs, M., Korabecny, J., Jun, D., Hodny, Z., Bartek, J., & Kuca, K. (2015). Phosphatidylinositol 3-kinase (PI3K) and phosphatidylinositol 3-kinase-related kinase (PIKK) inhibitors: Importance of the Morpholine ring. Journal of Medicinal Chemistry, 58(1), 41-71. https://doi.org/10.1021/jm501026z

Antonioli, L., Blandizzi, C., Csoka, B., Pacher, P., & Hasko, G. (2015). Adenosine signalling in diabetes mellitus-Pathophysiology and therapeutic considerations. Nature Reviews. Endocrinology, 11(4), 228-241. https://doi.org/10.1038/nrendo.2015.10

Arauz, J., Moreno, M. G., Cortes-Reynosa, P., Salazar, E. P., & Muriel, P. (2013). Coffee attenuates fibrosis by decreasing the expression of TGF-beta and CTGF in a murine model of liver damage. Journal of Applied Toxicology, 33(9), 970-979. https://doi.org/10.1002/jat.2788

Arauz, J., Zarco, N., Segovia, J., Shibayama, M., Tsutsumi, V., & Muriel, P. (2014). Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-beta. European Journal of Gastroenterology & Hepatology, 26(2), 164-173. https://doi.org/10.1097/MEG.0b013e3283644e26

Arnaud, M. J. (1987). The pharmacology of caffeine. Progress in Drug Research, 31, 273-313. https://doi.org/10.1007/978-3-0348-9289-6_9

Arnaud, M. J. (1993). Components of coffee. Caffeine, Coffee, and Health, 43, 22.

Arnaud, M. J. (2011). Pharmacokinetics and metabolism of natural methylxanthines in animal and man. Handb Exp Pharmacol, (200), 33-91. https://doi.org/10.1007/978-3-642-13443-2_3

Arteaga, C. L. (2010). Clinical development of phosphatidylinositol-3 kinase pathway inhibitors. Current Topics in Microbiology and Immunology, 347, 189-208. https://doi.org/10.1007/82_2010_54

Back, S. A., Craig, A., Luo, N. L., Ren, J., Akundi, R. S., Ribeiro, I., & Rivkees, S. A. (2006). Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury. Annals of Neurology, 60(6), 696-705. https://doi.org/10.1002/ana.21008

Bai, X. C., Yan, Z., Wu, J. P., Li, Z. Q., & Yan, N. (2016). The central domain of RyR1 is the transducer for long-range allosteric gating of channel opening. Cell Research, 26(9), 995-1006. https://doi.org/10.1038/cr.2016.89

Banerjee, P., Ali, Z., Levine, B., & Fowler, D. R. (2014). Fatal caffeine intoxication: A series of eight cases from 1999 to 2009. Journal of Forensic Sciences, 59(3), 865-868. https://doi.org/10.1111/1556-4029.12387

Barletta, K. E., Ley, K., & Mehrad, B. (2012). Regulation of neutrophil function by adenosine. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(4), 856-864. https://doi.org/10.1161/ATVBAHA.111.226845

Beauchamp, G., Amaducci, A., & Cook, M. (2017). Caffeine toxicity: A brief review and update. Clinical Pediatric Emergency Medicine, 18(3), 197-202. https://doi.org/10.1016/j.cpem.2017.07.002

Belibi, F. A., Wallace, D. P., Yamaguchi, T., Christensen, M., Reif, G., & Grantham, J. J. (2002). The effect of caffeine on renal epithelial cells from patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol, 13(11), 2723-2729. https://doi.org/10.1097/01.asn.0000025282.48298.7b

Benowitz, N. L. (1990). Clinical pharmacology of caffeine. Annual Review of Medicine, 41(1), 277-288.

Bertasi, R. A. O., Humeda, Y., Bertasi, T. G. O., Zins, Z., Kimsey, J., & Pujalte, G. (2021). Caffeine intake and mental health in college students. Cureus, 13(4), e14313. https://doi.org/10.7759/cureus.14313

Bezprozvanny, I., Bezprozvannaya, S., & Ehrlich, B. E. (1994). Caffeine-induced inhibition of inositol(1,4,5)-trisphosphate-gated calcium channels from cerebellum. Molecular Biology of the Cell, 5(1), 97-103. https://doi.org/10.1091/mbc.5.1.97

Bioh, G., Gallagher, M. M., & Prasad, U. (2013). Survival of a highly toxic dose of caffeine. BML Case Reports, 2013, bcr2012007454. https://doi.org/10.1136/bcr-2012-007454

Bishop, N. C., Fitzgerald, C., Porter, P. J., Scanlon, G. A., & Smith, A. C. (2005). Effect of caffeine ingestion on lymphocyte counts and subset activation in vivo following strenuous cycling. European Journal of Applied Physiology, 93(5-6), 606-613. https://doi.org/10.1007/s00421-004-1271-6

Blanchard, J. (1982). Protein binding of caffeine in young and elderly males. Journal of Pharmaceutical Sciences, 71(12), 1415-1418. https://doi.org/10.1002/jps.2600711229

Blanchard, J., & Sawers, S. J. (1983). Comparative pharmacokinetics of caffeine in young and elderly men. Journal of Pharmacokinetics and Biopharmaceutics, 11(2), 109-126. https://doi.org/10.1007/BF01061844

Blanchard, J., & Sawyers, S. J. (1983). The absolute bioavailability of caffeine in man. European Journal of Clinical Pharmacology, 24(1), 93-98.

Block, W. D., Merkle, D., Meek, K., & Lees-Miller, S. P. (2004). Selective inhibition of the DNA-dependent protein kinase (DNA-PK) by the radiosensitizing agent caffeine. Nucleic Acids Research, 32(6), 1967-1972. https://doi.org/10.1093/nar/gkh508

Bode, A. M., & Dong, Z. (2007). The enigmatic effects of caffeine in cell cycle and cancer. Cancer Letters, 247(1), 26-39. https://doi.org/10.1016/j.canlet.2006.03.032

Bologa, M., Tang, B., Klein, J., Tesoro, A., & Koren, G. (1991). Pregnancy-induced changes in drug metabolism in epileptic women. Journal of Pharmacology and Experimental Therapeutics, 257(2), 735-740.

Bonati, M., Latini, R., Galletti, F., Young, J. F., Tognoni, G., & Garattini, S. (1982). Caffeine disposition after oral doses. Clinical Pharmacology and Therapeutics, 32(1), 98-106. https://doi.org/10.1038/clpt.1982.132

Bonsignore, A., Sblano, S., Pozzi, F., Ventura, F., Dell'Erba, A., & Palmiere, C. (2014). A case of suicide by ingestion of caffeine. Forensic Science, Medicine, and Pathology, 10(3), 448-451. https://doi.org/10.1007/s12024-014-9571-6

Bosanac, I., Alattia, J. R., Mal, T. K., Chan, J., Talarico, S., Tong, F. K., Tong, K. I., Yoshikawa, F., Furuichi, T., Iwai, M., Michikawa, T., Mikoshiba, K., & Ikura, M. (2002). Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature, 420(6916), 696-700. https://doi.org/10.1038/nature01268

Boulenger, J. P., & Marangos, P. J. (1989). Caffeine withdrawal affects central adenosine receptors but not benzodiazepine receptors. Journal of Neural Transmission/General Section JNT, 78(1), 9-15.

Boulenger, J. P., Patel, J., Post, R. M., Parma, A. M., & Marangos, P. J. (1983). Chronic caffeine consumption increases the number of brain adenosine receptors. Life Sciences, 32(10), 1135-1142. https://doi.org/10.1016/0024-3205(83)90119-4

Brachtel, D., & Richter, E. (1988). Effect of altered gastric emptying on caffeine absorption. Zeitschrift für Gastroenterologie, 26(5), 245-251.

Brackett, L. E., & Daly, J. W. (1991). Relaxant effects of adenosine analogs on Guinea pig trachea in vitro: Xanthine-sensitive and xanthine-insensitive mechanisms. The Journal of Pharmacology and Experimental Therapeutics, 257(1), 205-213.

Bresciani, L., Calani, L., Bruni, R., Brighenti, F., & Del Rio, D. (2014). Phenolic composition, caffeine content and antioxidant capacity of coffee silverskin. Food Research International, 61, 196-201.

Brown, N. J., Ryder, D., & Nadeau, J. (1993). Caffeine attenuates the renal vascular-response to angiotensin-ii infusion. Hypertension, 22(6), 847-852. https://doi.org/10.1161/01.Hyp.22.6.847

Brumbaugh, K. M., Otterness, D. M., Geisen, C., Oliveira, V., Brognard, J., Li, X., Lejeune, F., Tibbetts, R. S., Maquat, L. E., & Abraham, R. T. (2004). The mRNA surveillance protein hSMG-1 functions in genotoxic stress response pathways in mammalian cells. Molecular Cell, 14(5), 585-598. https://doi.org/10.1016/j.molcel.2004.05.005

Buch, S., Ye, Y., & Haacke, E. M. (2017). Quantifying the changes in oxygen extraction fraction and cerebral activity caused by caffeine and acetazolamide. Journal of Cerebral Blood Flow and Metabolism, 37(3), 825-836. https://doi.org/10.1177/0271678X16641129

Burg, A. W. (1975). Physiological disposition of caffeine. Drug Metabolism Reviews, 4(2), 199-228. https://doi.org/10.3109/03602537508993756

Burnstock, G., & Novak, I. (2012). Purinergic signalling in the pancreas in health and disease. The Journal of Endocrinology, 213(2), 123-141. https://doi.org/10.1530/JOE-11-0434

Butler, M. A., Lang, N. P., Young, J. F., Caporaso, N. E., Vineis, P., Hayes, R. B., Teitel, C. H., Massengill, J. P., Lawsen, M. F., & Kadlubar, F. F. (1992). Determination of Cyp1a2 and Nat2 phenotypes in human-populations by analysis of caffeine urinary metabolites. Pharmacogenetics, 2(3), 116-127. https://doi.org/10.1097/00008571-199206000-00003

Byrne, E. M., Johnson, J., McRae, A. F., Nyholt, D. R., Medland, S. E., Gehrman, P. R., Heath, A. C., Madden, P. A. F., Montgomery, G. W., Chenevix-Trench, G., & Martin, N. G. (2012). A genome-wide association study of caffeine-related sleep disturbance: Confirmation of a role for a common variant in the adenosine receptor. Sleep, 35(7), 967-975. https://doi.org/10.5665/sleep.1962

Cabral-Miranda, F., Serfaty, C. A., & Campello-Costa, P. (2011). A time-dependent effect of caffeine upon lesion-induced plasticity. Neuroscience Research, 71(1), 99-102. https://doi.org/10.1016/j.neures.2011.05.018

Callahan, M. M., Robertson, R. S., Arnaud, M. J., Branfman, A. R., McComish, M. F., & Yesair, D. W. (1982). Human metabolism of [1-methyl-14C]- and [2-14C]caffeine after oral administration. Drug Metabolism and Disposition, 10(4), 417-423.

Campana, C., Griffin, P. L., & Simon, E. L. (2014). Caffeine overdose resulting in severe rhabdomyolysis and acute renal failure. American Journal of Emergency Medicine, 32(1), 111.e113-4. https://doi.org/10.1016/j.ajem.2013.08.042

Cappelletti, S., Piacentino, D., Sani, G., & Aromatario, M. (2015). Caffeine: Cognitive and physical performance enhancer or psychoactive drug? Current Neuropharmacology, 13(1), 71-88. https://doi.org/10.2174/1570159X13666141210215655

CARE Study Group. (2008). Maternal caffeine intake during pregnancy and risk of fetal growth restriction: A large prospective observational study. BMJ, 337, a2332. https://doi.org/10.1136/bmj.a2332

Carrageta, D. F., Dias, T. R., Alves, M. G., Oliveira, P. F., Monteiro, M. P., & Silva, B. M. (2018). Anti-obesity potential of natural methylxanthines. Journal of Functional Foods, 43, 84-94. https://doi.org/10.1016/j.jff.2018.02.001

Carrillo, J. A., & Benitez, J. (2000). Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clinical Pharmacokinetics, 39(2), 127-153. https://doi.org/10.2165/00003088-200039020-00004

Chan, E. S., Fernandez, P., & Cronstein, B. N. (2007). Adenosine in inflammatory joint diseases. Purinergic Signal, 3((1-2)), 145-152. https://doi.org/10.1007/s11302-006-9046-7

Chaudhary, N. S., Grandner, M. A., Jackson, N. J., & Chakravorty, S. (2016). Caffeine consumption, insomnia, and sleep duration: Results from a nationally representative sample. Nutrition, 32(11-12), 1193-1199. https://doi.org/10.1016/j.nut.2016.04.005

Chavez-Valdez, R., Ahlawat, R., Wills-Karp, M., & Gauda, E. B. (2016). Mechanisms of modulation of cytokine release by human cord blood monocytes exposed to high concentrations of caffeine. Pediatric Research, 80(1), 101-109. https://doi.org/10.1038/pr.2016.50

Chen, J. F. (2014). Adenosine receptor control of cognition in normal and disease. International Review of Neurobiology, 119, 257-307. https://doi.org/10.1016/B978-0-12-801022-8.00012-X

Chen, J. F. (2019). Caffeine and Parkinson's disease: From molecular targets to epidemiology and clinical trials. In A. Farah (Ed.), Coffee: Consumption and Health Implications (pp. 171-195). Royal Society of Chemistry. https://doi.org/10.1039/9781788015028

Chen, L. W., Wu, Y., Neelakantan, N., Chong, M. F. F., Pan, A., & van Dam, R. M. (2014). Maternal caffeine intake during pregnancy is associated with risk of low birth weight: A systematic review and dose-response meta-analysis. BMC Medicine, 12, 174. https://doi.org/10.1186/s12916-014-0174-6

Chen, S., Wu, Q., Zhong, D., Li, C., & Du, L. (2020). Caffeine prevents hyperoxia-induced lung injury in neonatal mice through NLRP3 inflammasome and NF-kappaB pathway. Respiratory Research, 21(1), 140. https://doi.org/10.1186/s12931-020-01403-2

Chen, X., Gawryluk, J. W., Wagener, J. F., Ghribi, O., & Geiger, J. D. (2008). Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease. Journal of Neuroinflammation, 5, 12. https://doi.org/10.1186/1742-2094-5-12

Chen, X., Ghribi, O., & Geiger, J. D. (2010). Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer's and Parkinson's diseases. Journal of Alzheimer's Disease, 20(Suppl 1), S127-S141. https://doi.org/10.3233/JAD-2010-1376

Chen, X., Lan, X., Roche, I., Liu, R., & Geiger, J. D. (2008). Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum. Journal of Neurochemistry, 107(4), 1147-1157. https://doi.org/10.1111/j.1471-4159.2008.05697.x

Cheng, Y.-C., Ding, Y.-M., Hueng, D.-Y., Chen, J.-Y., & Chen, Y. (2016). Caffeine suppresses the progression of human glioblastoma via cathepsin B and MAPK signaling pathway. The Journal of Nutritional Biochemistry, 33, 63-72. https://doi.org/10.1016/j.jnutbio.2016.03.004

Chiang, H.-M., Chen, C.-W., Chen, C.-C., Wang, H.-W., Jhang, J.-H., Huang, Y.-H., & Wen, K.-C. (2015). Role of coffea arabica extract and related compounds in preventing photoaging and photodamage of the skin. In Coffee in health and disease prevention (pp. 523-530). Elsevier.

Chiang, W. F., Liao, M. T., Cheng, C. J., & Lin, S. H. (2014). Rhabdomyolysis induced by excessive coffee drinking. Human & Experimental Toxicology, 33(8), 878-881. https://doi.org/10.1177/0960327113510536

Childs, E., Hohoff, C., Deckert, J., Xu, K., Badner, J., & De Wit, H. (2008). Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology, 33(12), 2791-2800.

Chvasta, T. E., & Cooke, A. R. (1971). Emptying and absorption of caffeine from the human stomach. Gastroenterology, 61(6), 838-843.

Clark, I., & Landolt, H. P. (2017). Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials. Sleep Medicine Reviews, 31, 70-78. https://doi.org/10.1016/j.smrv.2016.01.006

Clevers, H., & Nusse, R. (2012). Wnt/β-catenin signaling and disease. Cell, 149(6), 1192-1205.

Coffer, P. J., Jin, J., & Woodgett, J. R. (1998). Protein kinase B (c-Akt): A multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochemical Journal, 335, 1-13.

Coleman, R. M., Roffwarg, H. P., Kennedy, S. J., Guilleminault, C., Cinque, J., Cohn, M. A., & Dement, W. C. (1982). Sleep-wake disorders based on a Polysomnographic diagnosis - A National Cooperative Study. JAMA - Journal of the American Medical Association, 247(7), 997-1003. https://doi.org/10.1001/jama.247.7.997

Conde, S. V., Monteiro, E. C., Obeso, A., & Gonzalez, C. (2009). Adenosine in peripheral chemoreception: New insights into a historically overlooked molecule - invited article. Arterial Chemoreceptors, 648, 145-159. https://doi.org/10.1007/978-90-481-2259-2_17

Connolly, S., & Kingsbury, T. J. (2010). Caffeine modulates CREB-dependent gene expression in developing cortical neurons. Biochemical and Biophysical Research Communications, 397(2), 152-156. https://doi.org/10.1016/j.bbrc.2010.05.054

Cornelis, M. C., Byrne, E. M., Esko, T., Nalls, M. A., Ganna, A., Paynter, N., Monda, K. L., Amin, N., Fischer, K., Renstrom, F., Ngwa, J. S., Huikari, V., Cavadino, A., Nolte, I. M., Teumer, A., Yu, K., Marques-Vidal, P., Rawal, R., Manichaikul, A., … Chasman, D. I. (2015). Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Molecular Psychiatry, 20(5), 647-656. https://doi.org/10.1038/mp.2014.107

Cornelis, M. C., El-Sohemy, A., & Campos, H. (2007). Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. The American Journal of Clinical Nutrition, 86(1), 240-244.

Cornelis, M. C., Kacprowski, T., Menni, C., Gustafsson, S., Pivin, E., Adamski, J., Artati, A., Eap, C. B., Ehret, G., Friedrich, N., Ganna, A., Guessous, I., Homuth, G., Lind, L., Magnusson, P. K., Mangino, M., Pedersen, N. L., Pietzner, M., Suhre, K., … Ingelsson, E. (2016). Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior. Human Molecular Genetics, 25(24), 5472-5482. https://doi.org/10.1093/hmg/ddw334

Cornelis, M. C., Monda, K. L., Yu, K., Paynter, N., Azzato, E. M., Bennett, S. N., Berndt, S. I., Boerwinkle, E., Chanock, S., Chatterjee, N., Couper, D., Curhan, G., Heiss, G., Hu, F. B., Hunter, D. J., Jacobs, K., Jensen, M. K., Kraft, P., Landi, M. T., … Caporaso, N. E. (2011). Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) As determinants of habitual caffeine consumption. PLoS Genetics, 7(4), e1002033. https://doi.org/10.1371/journal.pgen.1002033

Cortez, D. (2003). Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) protein kinases. Journal of Biological Chemistry, 278(39), 37139-37145. https://doi.org/10.1074/jbc.M307088200

Costa, M. S., Botton, P. H., Mioranzza, S., Ardais, A. P., Moreira, J. D., Souza, D. O., & Porciuncula, L. O. (2008). Caffeine improves adult mice performance in the object recognition task and increases BDNF and TrkB independent on phospho-CREB immunocontent in the hippocampus. Neurochemistry International, 53(3-4), 89-94. https://doi.org/10.1016/j.neuint.2008.06.006

Crestani, F., Low, K., Keist, R., Mandelli, M., Mohler, H., & Rudolph, U. (2001). Molecular targets for the myorelaxant action of diazepam. Molecular Pharmacology, 59(3), 442-445. https://doi.org/10.1124/mol.59.3.442

Cui, W. Q., Wang, S. T., Pan, D., Chang, B., & Sang, L. X. (2020). Caffeine and its main targets of colorectal cancer. World J Gastrointest Oncol, 12(2), 149-172. https://doi.org/10.4251/wjgo.v12.i2.149

Cunha, R. A., & Agostinho, P. M. (2010). Chronic caffeine consumption prevents memory disturbance in different animal models of memory decline. Journal of Alzheimers Disease, 20(Suppl 1), S95-S116. https://doi.org/10.3233/JAD-2010-1408

Cunnington, D., Junge, M. F., & Fernando, A. T. (2013). Insomnia: Prevalence, consequences and effective treatment. Medical Journal of Australia, 199(8), S36-S40. https://doi.org/10.5694/mja13.10718

Curhan, G. C., Willett, W. C., Rimm, E. B., Spiegelman, D., & Stampfer, M. J. (1996). Prospective study of beverage use and the risk of kidney stones. American Journal of Epidemiology, 143(3), 240-247. https://doi.org/10.1093/oxfordjournals.aje.a008734

Curigliano, G., & Shah, R. R. (2019). Safety and tolerability of Phosphatidylinositol-3-kinase (PI3K) inhibitors in oncology. Drug Safety, 42(2), 247-262. https://doi.org/10.1007/s40264-018-0778-4

Da Silva, R. S. (2011). Chapter 27 - Caffeine. In R. C. Gupta (Ed.), Reproductive and developmental toxicology (pp. 355-364). Academic Press.

Daly, J. W. (1993). Mechanism of action of caffeine. In S. Garattini (Ed.), Caffeine, coffee, and health (pp. 97-150). Raven Press, Ltd.

Daly, J. W. (2007). Caffeine analogs: Biomedical impact. Cellular and Molecular Life Sciences, 64(16), 2153-2169.

Daly, J. W., Shi, D., Nikodijevic, O., & Jacobson, K. A. (1994). The role of adenosine receptors in the central action of caffeine. Pharmacopsychoecologia, 7(2), 201-213.

Daval, J. L., Deckert, J., Weiss, S. R., Post, R. M., & Marangos, P. J. (1989). Upregulation of adenosine A1 receptors and forskolin binding sites following chronic treatment with caffeine or carbamazepine: A quantitative autoradiographic study. Epilepsia, 30(1), 26-33. https://doi.org/10.1111/j.1528-1157.1989.tb05276.x

Davies, S., Lee, T., Ramsey, J., Dargan, P. I., & Wood, D. M. (2012). Risk of caffeine toxicity associated with the use of ‘highs’ (novel psychoactive substances). European Journal of Clinical Pharmacology, 68(4), 435-439. https://doi.org/10.1007/s00228-011-1144-y

Davoodi, S. H., Hajimiresmaiel, S. J., Ajami, M., Mohseni-Bandpei, A., Ayatollahi, S. A., Dowlatshahi, K., Javedan, G., & Pazoki-Toroudi, H. (2014). Caffeine treatment prevented from weight regain after calorie shifting diet induced weight loss. Iran J Pharm Res, 13(2), 707-718.

de Angelis, L., Bertolissi, M., Nardini, G., Traversa, U., & Vertua, R. (1982). Interaction of caffeine with benzodiazepines: Behavioral effects in mice. Archives Internationales de Pharmacodynamie et de Thérapie, 255(1), 89-102.

Delhaye, S., & Bardoni, B. (2021). Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders. Molecular Psychiatry, 26(9), 4570-4582. https://doi.org/10.1038/s41380-020-00997-9

DePaula, J., & Farah, A. (2019). Caffeine consumption through coffee: Content in the beverage, metabolism, health benefits and risks. Beverages, 5(2), 37. https://doi.org/10.3390/beverages5020037

des Georges, A., Clarke, O. B., Zalk, R., Yuan, Q., Condon, K. J., Grassucci, R. A., Hendrickson, W. A., Marks, A. R., & Frank, J. (2016). Structural basis for gating and activation of RyR1. Cell, 167(1), 145-157.e17. https://doi.org/10.1016/j.cell.2016.08.075

Desfrere, L., Olivier, P., Schwendimann, L., Verney, C., & Gressens, P. (2007). Transient inhibition of astrocytogenesis in developing mouse brain following postnatal caffeine exposure. Pediatric Research, 62(5), 604-609.

Deslandes, A. C., Veiga, H., Cagy, M., Piedade, R., Pompeu, F., & Ribeiro, P. (2005). Effects of caffeine on the electrophysiological, cognitive and motor responses of the central nervous system. Brazilian Journal of Medical and Biological Research, 38(7), 1077-1086. https://doi.org/10.1590/S0100-879x2005000700011

Di Martino, E., Bocchetta, E., Tsuji, S., Mukai, T., Harris, R. A., Blomgren, K., & Ådén, U. J. M. N. (2020). Defining a time window for Neuroprotection and glia modulation by caffeine after neonatal hypoxia-Ischaemia (pp. 1-12). Nature Publishing Group.

Domaszewski, P., Pakosz, P., Konieczny, M., Bączkowicz, D., & Sadowska-Krępa, E. (2021). Caffeine-induced effects on human skeletal muscle contraction time and maximal displacement measured by tensiomyography. Nutrients, 13(3), 815.

Dong, S., Kong, J., Kong, J., Shen, Q., Kong, F., Sun, W., & Zheng, L. (2015). Low concentration of caffeine inhibits the progression of the hepatocellular carcinoma via Akt Signaling pathway. Anti-Cancer Agents in Medicinal Chemistry, 15(4), 484-492. https://doi.org/10.2174/1871520615666150209110832

Dorne, J. L., Walton, K., & Renwick, A. G. (2001). Uncertainty factors for chemical risk assessment. Human variability in the pharmacokinetics of CYP1A2 probe substrates. Food and Chemical Toxicology, 39(7), 681-696. https://doi.org/10.1016/s0278-6915(01)00005-9

Downward, J. (1998). Mechanisms and consequences of activation of protein kinase B/Akt. Current Opinion in Cell Biology, 10(2), 262-267. https://doi.org/10.1016/s0955-0674(98)80149-x

Dulloo, A. G. (2011). The search for compounds that stimulate thermogenesis in obesity management: From pharmaceuticals to functional food ingredients. Obesity Reviews, 12(10), 866-883. https://doi.org/10.1111/j.1467-789X.2011.00909.x

Dulson, D. K., & Bishop, N. C. (2016). Effect of a high and low dose of caffeine on human lymphocyte activation in response to antigen stimulation. Applied Physiology, Nutrition, and Metabolism, 41(2), 224-227. https://doi.org/10.1139/apnm-2015-0456

Dumpa, V., Nielsen, L., Wang, H., & Kumar, V. H. S. (2019). Caffeine is associated with improved alveolarization and angiogenesis in male mice following hyperoxia induced lung injury. BMC Pulmonary Medicine, 19(1), 138. https://doi.org/10.1186/s12890-019-0903-x

Effendi, W. I., Nagano, T., Kobayashi, K., & Nishimura, Y. (2020). Focusing on adenosine receptors as a potential targeted therapy in human diseases. Cell, 9(3), 785. https://doi.org/10.3390/cells9030785

Eini, H., Frishman, V., Yulzari, R., Kachko, L., Lewis, E. C., Chaimovitz, C., & Douvdevani, A. (2015). Caffeine promotes anti-tumor immune response during tumor initiation: Involvement of the adenosine A2A receptor. Biochemical Pharmacology, 98(1), 110-118. https://doi.org/10.1016/j.bcp.2015.08.092

Ekstrom, J. L., Pauly, T. A., Carty, M. D., Soeller, W. C., Culp, J., Danley, D. E., Hoover, D. J., Treadway, J. L., Gibbs, E. M., Fletterick, R. J., Day, Y. S. N., Myszka, D. G., & Rath, V. L. (2002). Structure-activity analysis of the purine binding site of human liver glycogen phosphorylase. Chemistry & Biology, 9(8), 915-924. https://doi.org/10.1016/s1074-5521(02)00186-2

El-Din, H. M. N. (2011). Characterization and caffeine release properties of N-isopropylacrylamide/Hydroxypropyl methacrylate copolymer hydrogel synthesized by gamma radiation. Journal of Applied Polymer Science, 119(1), 577-585. https://doi.org/10.1002/app.32675

Elferink, J. G. R., & Dekoster, B. M. (1995). Ryanodine as inhibitor of chemotactic peptide-induced Chemotaxis in human neutrophils. Biochemical Pharmacology, 50(7), 975-979. https://doi.org/10.1016/0006-2952(95)00222-L

Eltzschig, H. K., Sitkovsky, M. V., & Robson, S. C. (2012). Purinergic signaling during inflammation. The New England Journal of Medicine, 367(24), 2322-2333. https://doi.org/10.1056/NEJMra1205750

Erblang, M., Drogou, C., Gomez-Merino, D., Metlaine, A., Boland, A., Deleuze, J. F., Thomas, C., Sauvet, F., & Chennaoui, M. (2019). The impact of genetic variations in ADORA2A in the association between caffeine consumption and sleep. Genes, 10(12), 1021. https://doi.org/10.3390/genes10121021

Espinosa, J., Rocha, A., Nunes, F., Costa, M. S., Schein, V., Kazlauckas, V., Kalinine, E., Souza, D. O., Cunha, R. A., & Porciuncula, L. O. (2013). Caffeine consumption prevents memory impairment, neuronal damage, and adenosine A2A receptors upregulation in the hippocampus of a rat model of sporadic dementia. Journal of Alzheimers Disease, 34(2), 509-518. https://doi.org/10.3233/JAD-111982

Evripioti, A. A., Ortega-Prieto, A. M., Skelton, J. K., Bazot, Q., & Dorner, M. (2019). Phosphodiesterase-induced cAMP degradation restricts hepatitis B virus infection. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 374(1773), 20180292. https://doi.org/10.1098/rstb.2018.0292

Fabiani, C., Murray, A. P., Corradi, J., & Antollini, S. S. (2018). A novel pharmacological activity of caffeine in the cholinergic system. Neuropharmacology, 135, 464-473. https://doi.org/10.1016/j.neuropharm.2018.03.041

Fenster, L., Eskenazi, B., Windham, G. C., & Swan, S. H. (1991). Caffeine consumption during pregnancy and fetal growth. American Journal of Public Health, 81(4), 458-461.

Ferraro, P. M., Taylor, E. N., Gambaro, G., & Curhan, G. C. (2014). Caffeine intake and the risk of kidney stones. The American Journal of Clinical Nutrition, 100(6), 1596-1603. https://doi.org/10.3945/ajcn.114.089987

Ferre, S. (2008). An update on the mechanisms of the psychostimulant effects of caffeine. Journal of Neurochemistry, 105(4), 1067-1079. https://doi.org/10.1111/j.1471-4159.2007.05196.x

Ferre, S. (2016). Mechanisms of the psychostimulant effects of caffeine: Implications for substance use disorders. Psychopharmacology, 233(10), 1963-1979. https://doi.org/10.1007/s00213-016-4212-2

Fletcher, D. K., & Bishop, N. C. (2012). Caffeine ingestion and antigen-stimulated human lymphocyte activation after prolonged cycling. Scandinavian Journal of Medicine & Science in Sports, 22(2), 249-258. https://doi.org/10.1111/j.1600-0838.2010.01223.x

Folcik, V. A., Smith, T., O'Bryant, S., Kawczak, J. A., Zhu, B., Sakurai, H., Kajiwara, A., Staddon, J. M., Glabinski, A., Chernosky, A. L., Tani, M., Johnson, J. M., Tuohy, V. K., Rubin, L. L., & Ransohoff, R. M. (1999). Treatment with BBB022A or rolipram stabilizes the blood-brain barrier in experimental autoimmune encephalomyelitis: An additional mechanism for the therapeutic effect of type IV phosphodiesterase inhibitors. Journal of Neuroimmunology, 97(1-2), 119-128. https://doi.org/10.1016/s0165-5728(99)00063-6

Forman, J., Aizer, A., & Young, C. R. (1997). Myocardial infarction resulting from caffeine overdose in an anorectic woman. Annals of Emergency Medicine, 29(1), 178-180. https://doi.org/10.1016/s0196-0644(97)70326-3

Foster, K. G., & Fingar, D. C. (2010). Mammalian target of rapamycin (mTOR): Conducting the cellular signaling symphony. Journal of Biological Chemistry, 285(19), 14071-14077. https://doi.org/10.1074/jbc.R109.094003

Foukas, L. C., Daniele, N., Ktori, C., Anderson, K. E., Jensen, J., & Shepherd, P. R. (2002). Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. Journal of Biological Chemistry, 277(40), 37124-37130. https://doi.org/10.1074/jbc.M202101200

Fredholm, B. B. (2010). Adenosine receptors as drug targets. Experimental Cell Research, 316(8), 1284-1288. https://doi.org/10.1016/j.yexcr.2010.02.004

Fredholm, B. B., Abbracchio, M. P., Burnstock, G., Dubyak, G. R., Harden, T. K., Jacobson, K. A., Schwabe, U., & Williams, M. (1997). Towards a revised nomenclature for P1 and P2 receptors. Trends in Pharmacological Sciences, 18(3), 79-82. https://doi.org/10.1016/s0165-6147(96)01038-3

Fredholm, B. B., Arslan, G., Halldner, L., Kull, B., Schulte, G., & Wasserman, W. (2000). Structure and function of adenosine receptors and their genes. Naunyn-Schmiedebergs Archives of Pharmacology, 362(4-5), 364-374. https://doi.org/10.1007/s002100000313

Fredholm, B. B., Battig, K., Holmen, J., Nehlig, A., & Zvartau, E. E. (1999). Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacological Reviews, 51(1), 83-133.

Fredholm, B. B., Ijzerman, A. P., Jacobson, K. A., Klotz, K. N., & Linden, J. (2001). International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacological Reviews, 53(4), 527-552.

Fredholm, B. B., Ijzerman, A. P., Jacobson, K. A., Linden, J., & Müller, C. E. (2011). International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors-An update. Pharmacological Reviews, 63(1), 1-34.

Frigerio, S., Strawbridge, R., & Young, A. H. (2021). The impact of caffeine consumption on clinical symptoms in patients with bipolar disorder: A systematic review. Bipolar Disorders, 23(3), 241-251. https://doi.org/10.1111/bdi.12990

Fukunaga, A. F., Alexander, G. E., & Stark, C. W. (2003). Characterization of the analgesic actions of adenosine: Comparison of adenosine and remifentanil infusions in patients undergoing major surgical procedures. Pain, 101(1-2), 129-138. https://doi.org/10.1016/s0304-3959(02)00321-4

Furtado, K. S., Polletini, J., Dias, M. C., Rodrigues, M. A., & Barbisan, L. F. (2014). Prevention of rat liver fibrosis and carcinogenesis by coffee and caffeine. Food and Chemical Toxicology, 64, 20-26. https://doi.org/10.1016/j.fct.2013.11.011

Futatsugi, A., Nakamura, T., Yamada, M. K., Ebisui, E., Nakamura, K., Uchida, K., Kitaguchi, T., Takahashi-Iwanaga, H., Noda, T., Aruga, J., & Mikoshiba, K. (2005). IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism. Science, 309(5744), 2232-2234. https://doi.org/10.1126/science.1114110

Gaeini, Z., Bahadoran, Z., Mirmiran, P., & Azizi, F. (2019). Tea, coffee, caffeine intake and the risk of cardio-metabolic outcomes: Findings from a population with low coffee and high tea consumption. Nutrition & Metabolism (London), 16, 28. https://doi.org/10.1186/s12986-019-0355-6

Gajewska, M., Paini, A., Benito, J. S., Burton, J., Worth, A., Urani, C., Briesen, H., & Schramm, K.-W. (2015). In vitro-to-in vivo correlation of the skin penetration, liver clearance and hepatotoxicity of caffeine. Food and Chemical Toxicology, 75, 39-49.

Gambardella, J., Lombardi, A., Morelli, M. B., Ferrara, J., & Santulli, G. (2020). Inositol 1,4,5-trisphosphate receptors in human disease: A comprehensive update. Journal ofClinical Medicine, 9(4), 1096. https://doi.org/10.3390/jcm9041096

Gans, J. M. D., Uiterwaal, C. S. P. M., van der Schouw, Y. T., Boer, J. M. A., Grobbee, D. E., Verschuren, W. M. M., & Beulens, J. W. J. (2010). Tea and coffee consumption and cardiovascular morbidity and mortality. Arteriosclerosis Thrombosis and Vascular Biology, 30(8), 1665-1667. https://doi.org/10.1161/Atvbaha.109.201939

Gardiner, C., Weakley, J., Burke, L. M., Roach, G. D., Sargent, C., Maniar, N., Townshend, A., & Halson, S. L. (2023). The effect of caffeine on subsequent sleep: A systematic review and meta-analysis. Sleep Medicine Reviews, 69, 101764. https://doi.org/10.1016/j.smrv.2023.101764

Gebhard, C., Holy, E. W., Camici, G. G., Akhmedov, A., Stämpfli, S. F., Stähli, B. E., von Rickenbach, B., Breitenstein, A., Greutert, H., Yang, Z., Lüscher, T. F., & Tanner, F. C. (2012). Caffeine induces endothelial tissue factor expression via phosphatidylinositol 3-kinase inhibition. Thrombosis and Haemostasis, 107(5), 884-894. https://doi.org/10.1160/Th11-09-0624

Geleijnse, J. M. (2008). Habitual coffee consumption and blood pressure: An epidemiological perspective. Vascular Health and Risk Management, 4(5), 963-970.

Georgiev, V., & Fredholm, B. B. (1993). Long-term caffeine treatment leads to a decreased susceptibility to NMDA-induced clonic seizures in mice without changes in adenosine A1 receptor number. Brain Research, 612(1-2), 271-277.

Ghai, G., Zimmerman, M. B., & Hopkins, M. F. (1987). Evidence for A1 and A2 adenosine receptors in Guinea pig trachea. Life Sciences, 41(10), 1215-1224. https://doi.org/10.1016/0024-3205(87)90199-8

Ghosh, A. K., Ghosh, C., & Gupta, A. (2013). A simple approach to detect caffeine in tea beverages. Journal of Agricultural and Food Chemistry, 61(16), 3814-3820.

Gleason, J. L., Sundaram, R., Mitro, S. D., Hinkle, S. N., Gilman, S. E., Zhang, C., Newman, R. B., Hunt, K. J., Skupski, D. W., Grobman, W. A., Nageotte, M., Robinson, M., Kannan, K., & Grantz, K. L. (2022). Association of Maternal Caffeine Consumption during Pregnancy with Child Growth. JAMA Network Open, 5(10), e2239609. https://doi.org/10.1001/jamanetworkopen.2022.39609

Godos, J., Pluchinotta, F. R., Marventano, S., Buscemi, S., Li Volti, G., Galvano, F., & Grosso, G. (2014). Coffee components and cardiovascular risk: Beneficial and detrimental effects. International Journal of Food Sciences and Nutrition, 65(8), 925-936. https://doi.org/10.3109/09637486.2014.940287

Goldfrank, L. R., & Hoffman, R. S. (2006). Goldfrank's toxicologic emergencies (Vol. 831). Appleton & Lange.

Gordillo-Bastidas, D., Oceguera-Contreras, E., Salazar-Montes, A., Gonzalez-Cuevas, J., Hernandez-Ortega, L. D., & Armendariz-Borunda, J. (2013). Nrf2 and Snail-1 in the prevention of experimental liver fibrosis by caffeine. World Journal of Gastroenterology, 19(47), 9020-9033. https://doi.org/10.3748/wjg.v19.i47.9020

Gottlieb, T. M., & Jackson, S. P. (1993). The DNA-dependent protein kinase: Requirement for DNA ends and association with Ku antigen. Cell, 72(1), 131-142.

Gramling, L., Kapoulea, E., & Murphy, C. (2018). Taste perception and caffeine consumption: An fMRI study. Nutrients, 11(1), 34. https://doi.org/10.3390/nu11010034

Gressner, O. A., Lahme, B., Rehbein, K., Siluschek, M., Weiskirchen, R., & Gressner, A. M. (2008). Pharmacological application of caffeine inhibits TGF-beta-stimulated connective tissue growth factor expression in hepatocytes via PPAR gamma and SMAD2/3-dependent pathways. Journal of Hepatology, 49(5), 758-767. https://doi.org/10.1016/j.jhep.2008.03.029

Griffeth, V. E., Perthen, J. E., & Buxton, R. B. (2011). Prospects for quantitative fMRI: Investigating the effects of caffeine on baseline oxygen metabolism and the response to a visual stimulus in humans. NeuroImage, 57(3), 809-816. https://doi.org/10.1016/j.neuroimage.2011.04.064

Griffin, C. E., 3rd, Kaye, A. M., Bueno, F. R., & Kaye, A. D. (2013). Benzodiazepine pharmacology and central nervous system-mediated effects. The Ochsner Journal, 13(2), 214-223.

Gross, M. E., & Booth, N. H. (2001). Tranquilizers, α2-adrenergic agonists, and related agents. Veterinary Pharmacology and Therapeutics, 41(56), 43-66.

Grosso, L. M., & Bracken, M. B. (2005). Caffeine metabolism, genetics, and perinatal outcomes: A review of exposure assessment considerations during pregnancy. Annals of Epidemiology, 15(6), 460-466.

Grzegorzewski, J., Bartsch, F., Koeller, A., & Koenig, M. (2022). Pharmacokinetics of caffeine: A systematic analysis of reported data for application in metabolic Phenotyping and liver function testing. Frontiers in Pharmacology, 12, 752826. https://doi.org/10.3389/fphar.2021.752826

Gu, L., Gonzalez, F. J., Kalow, W., & Tang, B. K. (1992). Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics, 2(2), 73-77.

Guessous, I., Eap, C. B., & Bochud, M. (2014). Blood pressure in relation to coffee and caffeine consumption. Current Hypertension Reports, 16(9), 468. https://doi.org/10.1007/s11906-014-0468-2

Hakooz, N. M. (2009). Caffeine metabolic ratios for the in vivo evaluation of CYP1A2, N-acetyltransferase 2, xanthine oxidase and CYP2A6 enzymatic activities. Current Drug Metabolism, 10(4), 329-338. https://doi.org/10.2174/138920009788499003

Hassanein, S. M., Gad, G. I., Ismail, R. I., & Diab, M. (2015). Effect of caffeine on preterm infants' cerebral cortical activity: An observational study. The Journal of Maternal-Fetal & Neonatal Medicine, 28(17), 2090-2095. https://doi.org/10.3109/14767058.2014.978757

Hatano, Y., Mizumoto, K., Yoshiyama, T., Yamamoto, M., & Iranami, H. (1995). Endothelium-dependent and-independent vasodilation of isolated rat aorta induced by caffeine. American Journal of Physiology-Heart and Circulatory Physiology, 269(5), H1679-H1684.

Hayes, J. M., Kantsadi, A. L., & Leonidas, D. D. (2014). Natural products and their derivatives as inhibitors of glycogen phosphorylase: Potential treatment for type 2 diabetes. Phytochemistry Reviews, 13(2), 471-498. https://doi.org/10.1007/s11101-014-9360-6

He, Z. W., Ma, W. Y., Hashimoto, T., Bode, A. M., Yang, C. S., & Dong, Z. G. (2003). Induction of apoptosis by caffeine is mediated by the p53, Bax, and caspase 3 pathways. Cancer Research, 63(15), 4396-4401.

Hedstrom, A. K., Mowry, E. M., Gianfrancesco, M. A., Shao, X., Schaefer, C. A., Shen, L., Olsson, T., Barcellos, L. F., & Alfredsson, L. (2016). High consumption of coffee is associated with decreased multiple sclerosis risk; results from two independent studies. Journal of Neurology Neurosurgery and Psychiatry, 87(5), 454-460. https://doi.org/10.1136/jnnp-2015-312176

Helal, M. G., Ayoub, S. E., Elkashefand, W. F., & Ibrahim, T. M. (2018). Caffeine affects HFD-induced hepatic steatosis by multifactorial intervention. Human & Experimental Toxicology, 37(9), 983-990. https://doi.org/10.1177/0960327117747026

Henke, B. R., & Sparks, S. M. (2006). Glycogen phosphorylase inhibitors. Mini Reviews in Medicinal Chemistry, 6(8), 845-857. https://doi.org/10.2174/138955706777934991

Herden, L., & Weissert, R. (2018). The impact of coffee and caffeine on multiple sclerosis compared to other neurodegenerative diseases. Frontiers in Nutrition, 5, 133. https://doi.org/10.3389/fnut.2018.00133

Herrmann-Frank, A., Luttgau, H. C., & Stephenson, D. G. (1999). Caffeine and excitation-contraction coupling in skeletal muscle: A stimulating story. Journal of Muscle Research and Cell Motility, 20(2), 223-237. https://doi.org/10.1023/a:1005496708505

Hill, R., & Lee, P. W. K. (2010). The DNA-dependent protein kinase (DNA-PK) more than just a case of making ends meet? Cell Cycle, 9(17), 3460-3469. https://doi.org/10.4161/cc.9.17.13043

Hoekstra, M. F. (1997). Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family. Current Opinion in Genetics & Development, 7(2), 170-175.

Holick, C. N., Smith, S. G., Giovannucci, E., & Michaud, D. S. (2010). Coffee, tea, caffeine intake, and risk of adult glioma in three prospective cohort studies. Cancer Epidemiology, Biomarkers & Prevention, 19(1), 39-47. https://doi.org/10.1158/1055-9965.EPI-09-0732

Holst, S. C., Bersagliere, A., Bachmann, V., Berger, W., Achermann, P., & Landolt, H. P. (2014). Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans. The Journal of Neuroscience, 34(2), 566-573. https://doi.org/10.1523/JNEUROSCI.4128-13.2014

Holstege, C. P., Hunter, Y., Baer, A. B., Savory, J., Bruns, D. E., & Boyd, J. C. (2003). Massive caffeine overdose requiring vasopressin infusion and hemodialysis. Journal of Toxicology. Clinical Toxicology, 41(7), 1003-1007. https://doi.org/10.1081/clt-120026526

Holtzman, S. G., Mante, S., & Minneman, K. P. (1991). Role of adenosine receptors in caffeine tolerance. Journal of Pharmacology and Experimental Therapeutics, 256(1), 62-68.

Honjo, S., Kono, S., Coleman, M. P., Shinchi, K., Sakurai, Y., Todoroki, I., Umeda, T., Wakabayashi, K., Imanishi, K., Nishikawa, H., Ogawa, S., Katsurada, M., Nakagawa, K., & Yoshizawa, N. (2001). Coffee consumption and serum aminotransferases in middle-aged Japanese men. Journal of Clinical Epidemiology, 54(8), 823-829. https://doi.org/10.1016/s0895-4356(01)00344-4

Horrigan, L., Diamond, M., Connor, T., & Kelly, J. P. (2003). Caffeine inhibits monocyte and neutrophil chemotaxis at concentrations relevant to normal human consumption. In Proceedings of the International Cytokine Society Annual Meeting (pp. 20-24). Dublin, Ireland.

Horrigan, L. A., Kelly, J. P., & Connor, T. J. (2004). Caffeine suppresses TNF-alpha production via activation of the cyclic AMP/protein kinase a pathway. International Immunopharmacology, 4(10-11), 1409-1417. https://doi.org/10.1016/j.intimp.2004.06.005

Horrigan, L. A., Kelly, J. P., & Connor, T. J. (2006). Immunomodulatory effects of caffeine: Friend or foe? Pharmacology & Therapeutics, 111(3), 877-892. https://doi.org/10.1016/j.pharmthera.2006.02.002

Hossain, S. J., Hamamoto, K., Aoshima, H., & Hara, Y. (2002). Effects of tea components on the response of GABA(A) receptors expressed in Xenopus oocytes. Journal of Agricultural and Food Chemistry, 50(14), 3954-3960. https://doi.org/10.1021/jf011607h

Hu, X. W., Li, X. M., Wang, A. M., Fu, Y. M., Zhang, F. J., Zeng, F., Cao, L. P., Long, H., Xiong, Y. H., Xu, J., & Li, J. (2022). Caffeine alleviates acute liver injury by inducing the expression of NEDD4L and deceasing GRP78 level via ubiquitination. Inflammation Research, 71(10-11), 1213-1227. https://doi.org/10.1007/s00011-022-01603-0

Huang, L., & Sperlagh, B. (2021). Caffeine consumption and schizophrenia: A highlight on adenosine receptor-independent mechanisms. Current Opinion in Pharmacology, 61, 106-113. https://doi.org/10.1016/j.coph.2021.09.003

Huang, W., Cane, M. C., Mukherjee, R., Szatmary, P., Zhang, X. Y., Elliott, V., Ouyang, Y., Chvanov, M., Latawiec, D., Wen, L., Booth, D. M., Haynes, A. C., Petersen, O. H., Tepikin, A. V., Criddle, D. N., & Sutton, R. (2017). Caffeine protects against experimental acute pancreatitis by inhibition of inositol 1,4,5-trisphosphate receptor-mediated Ca2+ release. Gut, 66(2), 301-313. https://doi.org/10.1136/gutjnl-2015-309363

Huang, Y. W., Wang, L. T., Zhang, M., Nie, Y., Yang, J. B., Meng, W. L., Wang, X. J., & Sheng, J. (2023). Caffeine can alleviate non-alcoholic fatty liver disease by augmenting LDLR expression via targeting EGFR. Food & Function, 14(7), 3269-3278. https://doi.org/10.1039/d2fo02701a

Huang, Z. L., Qu, W. M., Eguchi, N., Chen, J. F., Schwarzschild, M. A., Fredholm, B. B., Urade, Y., & Hayaishi, O. (2005). Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nature Neuroscience, 8(7), 858-859. https://doi.org/10.1038/nn1491

Ismail, T., Donati-Zeppa, S., Akhtar, S., Turrini, E., Layla, A., Sestili, P., & Fimognari, C. (2021). Coffee in cancer chemoprevention: An updated review. Expert Opinion on Drug Metabolism & Toxicology, 17(1), 69-85. https://doi.org/10.1080/17425255.2021.1839412

Jabbar, S. B., & Hanly, M. G. (2013). Fatal caffeine overdose: A case report and review of literature. The American Journal of Forensic Medicine and Pathology, 34(4), 321-324. https://doi.org/10.1097/PAF.0000000000000058

Jacobson, K. A., & Gao, Z. G. (2006). Adenosine receptors as therapeutic targets. Nature Reviews Drug Discovery, 5(3), 247-264. https://doi.org/10.1038/nrd1983

Jacobson, K. A., & Muller, C. E. (2016). Medicinal chemistry of adenosine, P2Y and P2X receptors. Neuropharmacology, 104, 31-49. https://doi.org/10.1016/j.neuropharm.2015.12.001

Jakobs, S., Fridrich, D., Hofem, S., Pahlke, G., & Eisenbrand, G. (2006). Natural flavonoids are potent inhibitors of glycogen phosphorylase. Molecular Nutrition & Food Research, 50(1), 52-57. https://doi.org/10.1002/mnfr.200500163

James, J. E. (2014). Caffeine and cognitive performance: Persistent methodological challenges in caffeine research. Pharmacology Biochemistry and Behavior, 124, 117-122. https://doi.org/10.1016/j.pbb.2014.05.019

Janda, C. Y., Waghray, D., Levin, A. M., Thomas, C., & Garcia, K. C. (2012). Structural basis of Wnt recognition by frizzled. Science, 337(6090), 59-64. https://doi.org/10.1126/science.1222879

Janicak, P. G. (2002). Molecular neuropharmacology: A foundation for clinical neuroscience. American Journal of Psychiatry, 159(7), 1251. https://doi.org/10.1176/appi.ajp.159.7.1251

Jaruvongvanich, V., Sanguankeo, A., Klomjit, N., & Upala, S. (2017). Effects of caffeine consumption in patients with chronic hepatitis C: A systematic review and meta-analysis. Clinics and Research in Hepatology and Gastroenterology, 41(1), 46-55. https://doi.org/10.1016/j.clinre.2016.05.012

Jin, D., Fan, J., Wang, L., Thompson, L. F., Liu, A., Daniel, B. J., Shin, T., Curiel, T. J., & Zhang, B. (2010). CD73 on tumor cells impairs antitumor T-cell responses: A novel mechanism of tumor-induced immune suppression. Cancer Research, 70(6), 2245-2255. https://doi.org/10.1158/0008-5472.CAN-09-3109

Jones, G. (2008). Caffeine and other sympathomimetic stimulants: Modes of action and effects on sports performance. Essays in Biochemistry, 44, 109-123. https://doi.org/10.1042/BSE0440109

Joulia, F., Coulange, M., Lemaitre, F., Costalat, G., Franceschi, F., Gariboldi, V., Nee, L., Fromonot, J., Bruzzese, L., Gravier, G., Kipson, N., Jammes, Y., Boussuges, A., Brignole, M., Deharo, J. C., & Guieu, R. (2013). Plasma adenosine release is associated with bradycardia and transient loss of consciousness during experimental breath-hold diving. International Journal of Cardiology, 168(5), E138-E141. https://doi.org/10.1016/j.ijcard.2013.08.053

Kakugawa, S., Langton, P. F., Zebisch, M., Howell, S., Chang, T. H., Liu, Y., Feizi, T., Bineva, G., O'Reilly, N., Snijders, A. P., Jones, E. Y., & Vincent, J. P. (2015). Notum deacylates Wnt proteins to suppress signalling activity. Nature, 519(7542), 187-192. https://doi.org/10.1038/nature14259

Kalow, W., & Tang, B. K. (1991). Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clinical Pharmacology & Therapeutics, 50(5-1), 508-519.

Kalow, W., & Tang, B. K. (1993). The use of caffeine for enzyme assays - A critical-appraisal. Clinical Pharmacology & Therapeutics, 53(5), 503-514. https://doi.org/10.1038/clpt.1993.63

Kamimori, G. H., Karyekar, C. S., Otterstetter, R., Cox, D. S., Balkin, T. J., Belenky, G. L., & Eddington, N. D. (2002). The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. International Journal of Pharmaceutics, 234(1-2), 159-167. https://doi.org/10.1016/S0378-5173(01)00958-9

Kanbay, M., Siriopol, D., Copur, S., Tapoi, L., Benchea, L., Kuwabara, M., Rossignol, P., Ortiz, A., Covic, A., & Afsar, B. (2021). Effect of coffee consumption on renal outcome: A systematic review and meta-analysis of clinical studies. Journal of Renal Nutrition, 31(1), 5-20. https://doi.org/10.1053/j.jrn.2020.08.004

Kang, S. S., Han, K. S., Ku, B. M., Lee, Y. K., Hong, J., Shin, H. Y., Almonte, A. G., Woo, D. H., Brat, D. J., Hwang, E. M., Yoo, S. H., Chung, C. K., Park, S. H., Paek, S. H., Roh, E. J., Lee, S., Park, J. Y., Traynelis, S. F., & Lee, C. J. (2010). Caffeine-mediated inhibition of calcium Release Channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks Glioblastoma invasion and extends survival. Cancer Research, 70(3), 1173-1183. https://doi.org/10.1158/0008-5472.Can-09-2886

Kapellou, A., King, A., Graham, C. A. M., Pilic, L., & Mavrommatis, Y. (2023). Genetics of caffeine and brain-related outcomes - A systematic review of observational studies and randomized trials. Nutrition Reviews, nuad029. https://doi.org/10.1093/nutrit/nuad029

Kaplan, G. B., Greenblatt, D. J., Ehrenberg, B. L., Goddard, J. E., Cotreau, M. M., Harmatz, J. S., & Shader, R. I. (1997). Dose-dependent pharmacokinetics and psychomotor effects of caffeine in humans. Journal of Clinical Pharmacology, 37(8), 693-703. https://doi.org/10.1002/j.1552-4604.1997.tb04356.x

Karadsheh, N., Kussie, P., & Linthicum, D. S. (1991). Inhibition of acetylcholinesterase by caffeine, anabasine, methyl pyrrolidine and their derivatives. Toxicology Letters, 55(3), 335-342. https://doi.org/10.1016/0378-4274(91)90015-X

Karuppagounder, S. S., Uthaythas, S., Govindarajulu, M., Ramesh, S., Parameshwaran, K., & Dhanasekaran, M. (2021). Caffeine, a natural methylxanthine nutraceutical, exerts dopaminergic neuroprotection. Neurochemistry International, 148, 105066. https://doi.org/10.1016/j.neuint.2021.105066

Kasvinsky, P. J., Fletterick, R. J., & Madsen, N. B. (1981). Regulation of the dephosphorylation of glycogen phosphorylase a and synthase b by glucose and caffeine in isolated hepatocytes. Canadian Journal of Biochemistry, 59(6), 387-395.

Katagiri, R., Asakura, K., Kobayashi, S., Suga, H., Sasaki, S., & Diets, T.-G. S. W. (2014). Low intake of vegetables, high intake of confectionary, and unhealthy eating habits are associated with poor sleep quality among middle-aged female Japanese workers. Journal of Occupational Health, 56(5), 359-368. https://doi.org/10.1539/joh.14-0051-OA

Kaufmann, W. K., Heffernan, T. P., Beaulieu, L. M., Doherty, S., Frank, A. R., Zhou, Y., Bryant, M. F., Zhou, T., Luche, D. D., Nikolaishvili-Feinberg, N., Simpson, D. A., & Cordeiro-Stone, M. (2003). Caffeine and human DNA metabolism: The magic and the mystery. Mutation Research, 532(1-2), 85-102. https://doi.org/10.1016/j.mrfmmm.2003.08.012

Keravis, T., & Lugnier, C. (2012). Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: Benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments. British Journal of Pharmacology, 165(5), 1288-1305. https://doi.org/10.1111/j.1476-5381.2011.01729.x

Kerrigan, S., & Lindsey, T. (2005). Fatal caffeine overdose: Two case reports. Forensic Science International, 153(1), 67-69. https://doi.org/10.1016/j.forsciint.2005.04.016

Khalaf, N., White, D., Kanwal, F., Ramsey, D., Mittal, S., Tavakoli-Tabasi, S., Kuzniarek, J., & el-Serag, H. B. (2015). Coffee and caffeine are associated with decreased risk of advanced hepatic fibrosis among patients with hepatitis C. Clinical Gastroenterology and Hepatology, 13(8), 1521-1531.e3. https://doi.org/10.1016/j.cgh.2015.01.030

Khondker, A., Dhaliwal, A., Alsop, R. J., Tang, J., Backholm, M., Shi, A. C., & Rheinstadter, M. C. (2017). Partitioning of caffeine in lipid bilayers reduces membrane fluidity and increases membrane thickness. Physical Chemistry Chemical Physics, 19(10), 7101-7111. https://doi.org/10.1039/c6cp08104e

Ko, Y. H., Shim, K. Y., Lee, S. Y., & Jang, C. G. (2018). Evodiamine reduces caffeine-induced sleep disturbances and excitation in mice. Biomol Ther (Seoul), 26(5), 432-438. https://doi.org/10.4062/biomolther.2017.146

Kogure, A., Sakane, N., Takakura, Y., Umekawa, T., Yoshioka, K., Nishino, H., Yamamoto, T., Kawada, T., Yoshikawa, T., & Yoshida, T. (2002). Effects of caffeine on the uncoupling protein family in obese yellow KK mice. Clinical and Experimental Pharmacology & Physiology, 29(5-6), 391-394. https://doi.org/10.1046/j.1440-1681.2002.03675.x

Kokubo, Y., Iso, H., Saito, I., Yamagishi, K., Yatsuya, H., Ishihara, J., Inoue, M., & Tsugane, S. (2013). The impact of green tea and coffee consumption on the reduced risk of stroke incidence in Japanese population: The Japan public health center-based study cohort. Stroke, 44(5), 1369-1374. https://doi.org/10.1161/STROKEAHA.111.677500

Kolahdouzan, M., & Hamadeh, M. J. (2017). The neuroprotective effects of caffeine in neurodegenerative diseases. CNS Neuroscience & Therapeutics, 23(4), 272-290. https://doi.org/10.1111/cns.12684

Kong, H., Jones, P. P., Koop, A., Zhang, L., Duff, H. J., & Chen, S. R. (2008). Caffeine induces Ca2+ release by reducing the threshold for luminal Ca2+ activation of the ryanodine receptor. The Biochemical Journal, 414(3), 441-452. https://doi.org/10.1042/BJ20080489

Konishi, Y., Hori, H., Ide, K., Katsuki, A., Atake, K., Igata, R., Kubo, T., Tominaga, H., Beppu, H., Asahara, T., & Yoshimura, R. (2018). Effect of single caffeine intake on neuropsychological functions in healthy volunteers: A double-blind placebo-controlled study. PLoS One, 13(10), e0202247. https://doi.org/10.1371/journal.pone.0202247

Koroglu, O. A., MacFarlane, P. M., Balan, K. V., Zenebe, W. J., Jafri, A., Martin, R. J., & Kc, P. (2014). Anti-inflammatory effect of caffeine is associated with improved lung function after lipopolysaccharide-induced Amnionitis. Neonatology, 106(3), 235-240. https://doi.org/10.1159/000363217

Kot, M., & Daniel, W. A. (2008). Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacological Reports, 60(6), 789-797.

Kumar, V. H. S., & Lipshultz, S. E. (2019). Caffeine and clinical outcomes in premature neonates. Children (Basel), 6(11), 118. https://doi.org/10.3390/children6110118

Kuwayama, H. (2012). Arachidonic acid enhances caffeine-induced cell death via caspase-independent cell death. Scientific Reports, 2, 577. https://doi.org/10.1038/srep00577

Landolt, H. P. (2008). Sleep homeostasis: A role for adenosine in humans? Biochemical Pharmacology, 75(11), 2070-2079. https://doi.org/10.1016/j.bcp.2008.02.024

Laplante, M., & Sabatini, D. M. (2009). mTOR signaling at a glance. Journal of Cell Science, 122(20), 3589-3594. https://doi.org/10.1242/jcs.051011

Lashley, T., Schott, J. M., Weston, P., Murray, C. E., Wellington, H., Keshavan, A., Foti, S. C., Foiani, M., Toombs, J., Rohrer, J. D., Heslegrave, A., & Zetterberg, H. (2018). Molecular biomarkers of Alzheimer's disease: Progress and prospects. Disease Models & Mechanisms, 11(5), dmm031781. https://doi.org/10.1242/dmm.031781

Lau, C. C., & Pardee, A. B. (1982). Mechanism by which caffeine potentiates lethality of nitrogen-Mustard. Proceedings of the National Academy of Sciences of the United States of America-Biological Sciences, 79(9), 2942-2946. https://doi.org/10.1073/pnas.79.9.2942

Laurent, C., Burnouf, S., Ferry, B., Batalha, V. L., Coelho, J. E., Baqi, Y., Malik, E., Mariciniak, E., Parrot, S., van der Jeugd, A., Faivre, E., Flaten, V., Ledent, C., D'Hooge, R., Sergeant, N., Hamdane, M., Humez, S., Müller, C. E., Lopes, L. V., … Blum, D. (2016). A2A adenosine receptor deletion is protective in a mouse model of Tauopathy. Molecular Psychiatry, 21(1), 97-107.

Lazarus, M., Oishi, Y., Bjorness, T. E., & Greene, R. W. (2019). Gating and the need for sleep: Dissociable effects of adenosine a(1) and a(2A) receptors. Frontiers in Neuroscience, 13, 740. https://doi.org/10.3389/fnins.2019.00740

Lazarus, M., Shen, H. Y., Cherasse, Y., Qu, W. M., Huang, Z. L., Bass, C. E., Winsky-Sommerer, R., Semba, K., Fredholm, B. B., Boison, D., Hayaishi, O., Urade, Y., & Chen, J. F. (2011). Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. The Journal of Neuroscience, 31(27), 10067-10075. https://doi.org/10.1523/JNEUROSCI.6730-10.2011

Lebeau, P. F., Byun, J. H., Platko, K., Saliba, P., Sguazzin, M., MacDonald, M. E., Paré, G., Steinberg, G. R., Janssen, L. J., Igdoura, S. A., Tarnopolsky, M. A., Wayne Chen, S. R., Seidah, N. G., Magolan, J., & Austin, R. C. (2022). Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance. Nature Communications, 13(1), 770. https://doi.org/10.1038/s41467-022-28240-9

Lee, J., Ha, J. H., Kim, S., Oh, Y., & Kim, S. W. (2002). Caffeine decreases the expression of Na+/K+-ATPase and the type 3 Na+/H+ exchanger in rat kidney. Clinical and Experimental Pharmacology & Physiology, 29(7), 559-563. https://doi.org/10.1046/j.1440-1681.2002.03697.x

Lee, K., Lindsey, A. S., Li, N., Gary, B., Andrews, J., Keeton, A. B., & Piazza, G. A. (2016). Beta-catenin nuclear translocation in colorectal cancer cells is suppressed by PDE10A inhibition, cGMP elevation, and activation of PKG. Oncotarget, 7(5), 5353-5365. https://doi.org/10.18632/oncotarget.6705

Leger, D., Poursain, B., Neubauer, D., & Uchiyama, M. (2008). An international survey of sleeping problems in the general population. Current Medical Research and Opinion, 24(1), 307-317. https://doi.org/10.1185/030079907x253771

Lelo, A., Miners, J. O., Robson, R. A., & Birkett, D. J. (1986). Quantitative assessment of caffeine partial clearances in man. British Journal of Clinical Pharmacology, 22(2), 183-186. https://doi.org/10.1111/j.1365-2125.1986.tb05247.x

Lemery, R., Pecarskie, A., Bernick, J., Williams, K., & Wells, G. A. (2015). A prospective placebo controlled randomized study of caffeine in patients with supraventricular tachycardia undergoing electrophysiologic testing. Journal of Cardiovascular Electrophysiology, 26(1), 1-6. https://doi.org/10.1111/jce.12504

Lempiainen, H., & Halazonetis, T. D. (2009). Emerging common themes in regulation of PIKKs and PI3Ks. EMBO Journal, 28(20), 3067-3073. https://doi.org/10.1038/emboj.2009.281

Leurs, L. J., Schouten, L. J., Goldbohm, R. A., & van den Brandt, P. A. (2010). Total fluid and specific beverage intake and mortality due to IHD and stroke in The Netherlands cohort study. British Journal of Nutrition, 104(8), 1212-1221. https://doi.org/10.1017/S0007114510001923

Levy, I., Horvath, A., Azevedo, M., de Alexandre, R. B., & Stratakis, C. A. (2011). Phosphodiesterase function and endocrine cells: Links to human disease and roles in tumor development and treatment. Current Opinion in Pharmacology, 11(6), 689-697. https://doi.org/10.1016/j.coph.2011.10.003

Li, Y. F., Ouyang, S. H., Tu, L. F., Wang, X., Yuan, W. L., Wang, G. E., Wu, Y. P., Duan, W. J., Yu, H. M., Fang, Z. Z., Kurihara, H., Zhang, Y., & He, R. R. (2018). Caffeine protects skin from oxidative stress-induced senescence through the activation of autophagy. Theranostics, 8(20), 5713-5730. https://doi.org/10.7150/thno.28778

Lin, Y. S., Weibel, J., Landolt, H. P., Santini, F., Slawik, H., Borgwardt, S., Cajochen, C., & Reichert, C. F. (2023). Brain activity during a working memory task after daily caffeine intake and caffeine withdrawal: A randomized double-blind placebo-controlled trial. Scientific Reports, 13(1), 1002. https://doi.org/10.1038/s41598-022-26808-5

Lin, Z., Jiang, D., Liu, P., Ge, Y., Moghekar, A., & Lu, H. (2022). Blood-brain barrier permeability in response to caffeine challenge. Magnetic Resonance in Medicine, 88(5), 2259-2266. https://doi.org/10.1002/mrm.29355

Liu, G. Y., & Sabatini, D. M. (2020). mTOR at the nexus of nutrition, growth, ageing and disease (vol 29, pg 145, 2020). Nature Reviews Molecular Cell Biology, 21(4), 246. https://doi.org/10.1038/s41580-020-0219-y

Liu, H., Zhou, Y., & Tang, L. (2017). Caffeine induces sustained apoptosis of human gastric cancer cells by activating the caspase-9/caspase-3 signalling pathway. Molecular Medicine Reports, 16(3), 2445-2454. https://doi.org/10.3892/mmr.2017.6894

Liu, P., Cheng, H., Roberts, T. M., & Zhao, J. J. (2009). Targeting the phosphoinositide 3-kinase pathway in cancer. Nature Reviews Drug Discovery, 8(8), 627-644. https://doi.org/10.1038/nrd2926

Liu, T. T., Behzadi, Y., Restom, K., Uludag, K., Lu, K., Buracas, G. T., Dubowitz, D. J., & Buxton, R. B. (2004). Caffeine alters the temporal dynamics of the visual BOLD response. NeuroImage, 23(4), 1402-1413. https://doi.org/10.1016/j.neuroimage.2004.07.061

Lo, W. T., Belabed, H., Kucukdisli, M., Metag, J., Roske, Y., Prokofeva, P., Ohashi, Y., Horatscheck, A., Cirillo, D., Krauss, M., Schmied, C., Neuenschwander, M., von Kries, J. P., Médard, G., Kuster, B., Perisic, O., Williams, R. L., Daumke, O., Payrastre, B., & Haucke, V. (2023). Development of selective inhibitors of phosphatidylinositol 3-kinase C2alpha. Nature Chemical Biology, 19(1), 18-27. https://doi.org/10.1038/s41589-022-01118-z

Lopes, J. P., Pliassova, A., & Cunha, R. A. (2019). The physiological effects of caffeine on synaptic transmission and plasticity in the mouse hippocampus selectively depend on adenosine A1 and A2A receptors. Biochemical Pharmacology, 166, 313-321. https://doi.org/10.1016/j.bcp.2019.06.008

Lopez, F., Miller, L. G., Greenblatt, D. J., Kaplan, G. B., & Shader, R. I. (1989). Interaction of caffeine with the GABAA receptor complex: Alterations in receptor function but not ligand binding. European Journal of Pharmacology, 172(6), 453-459. https://doi.org/10.1016/0922-4106(89)90028-x

Lucas, M., Mirzaei, F., Pan, A., Okereke, O. I., Willett, W. C., O'Reilly, E. J., Koenen, K., & Ascherio, A. (2011). Coffee, caffeine, and risk of depression among women. Archives of Internal Medicine, 171(17), 1571-1578. https://doi.org/10.1001/archinternmed.2011.393

Luciano, M., Zhu, G., Kirk, K. M., Gordon, S. D., Heath, A. C., Montgomery, G. W., & Martin, N. G. (2007). "No thanks, it keeps me awake": The genetics of coffee-attributed sleep disturbance. Sleep, 30(10), 1378-1386. https://doi.org/10.1093/sleep/30.10.1378

Lu'o'ng, K. V. Q., & Nguyen, L. T. H. (2015). The role of caffeine in neurodegenerative diseases possible genetic and cellular Signaling mechanisEms. In R. R. Watson & V. R. Preedy (Eds.), Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease: Prevention and Therapy (pp. 261-279). Academic Press. https://doi.org/10.1016/B978-0-12-411462-3.00028-X

Lv, X., Chen, Z., Li, J., Zhang, L., Liu, H., Huang, C., & Zhu, P. (2010). Caffeine protects against alcoholic liver injury by attenuating inflammatory response and oxidative stress. Inflammation Research, 59(8), 635-645. https://doi.org/10.1007/s00011-010-0176-6

Lymperopoulos, A., Brill, A., & McCrink, K. A. (2016). GPCRs of adrenal chromaffin cells & catecholamines: The plot thickens. The International Journal of Biochemistry & Cell Biology, 77(Pt B), 213-219. https://doi.org/10.1016/j.biocel.2016.02.003

Ma, Y., Pannicke, U., Schwarz, K., & Lieber, M. R. (2002). Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V (D) J recombination. Cell, 108(6), 781-794.

Mabunga, D. F. N., Gonzales, E. L. T., Kim, H. J., & Choung, S. Y. (2015). Treatment of GABA from fermented Rice germ ameliorates caffeine-induced sleep disturbance in mice. Biomolecules & Therapeutics, 23(3), 268-274. https://doi.org/10.4062/biomolther.2015.022

Madeira, M. H., Ortin-Martinez, A., Nadal-Nícolas, F., Ambrósio, A. F., Vidal-Sanz, M., Agudo-Barriuso, M., & Santiago, A. R. (2016). Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma. Scientific Reports, 6(1), 27532. https://doi.org/10.1038/srep27532

Madsen, N. B., Boyer, P. D., & Krebs, E. G. (1986). The enzymes (pp. 366-394). Academic Press.

Madsen, N. B., Shechosky, S., & Fletterick, R. J. (1983). Site-site interactions in glycogen Phosphorylase-B probed by ligands specific for each site. Biochemistry, 22(19), 4460-4465. https://doi.org/10.1021/bi00288a017

Maes, K., Missiaen, L., De Smet, P., Vanlingen, S., Callewaert, C., Parys, J. B., & De Smedt, H. (2000). Differential modulation of inositol 1,4,5-trisphosphate receptor type 1 and type 3 by ATP. Cell Calcium, 27(5), 257-267. https://doi.org/10.1054/ceca.2000.0121

Magkos, F., & Kavouras, S. A. (2005). Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action. Critical Reviews in Food Science and Nutrition, 45(7-8), 535-562. https://doi.org/10.1080/1040-830491379245

Mandel, H. G. (2002). Update on caffeine consumption, disposition and action. Food and Chemical Toxicology, 40(9), 1231-1234. https://doi.org/10.1016/S0278-6915(02)00093-5

Marangos, P. J., Boulenger, J. P., & Patel, J. (1984). Effects of chronic caffeine on brain adenosine receptors: Regional and ontogenetic studies. Life Sciences, 34(9), 899-907. https://doi.org/10.1016/0024-3205(84)90207-8

Marks, V., & Kelly, J. F. (1973). Absorption of caffeine from tea, coffee, and coca cola. Lancet, 1(7807), 827. https://doi.org/10.1016/s0140-6736(73)90625-9

Martin, W. H., Hoover, D. J., Armento, S. J., Stock, I. A., McPherson, R. K., Danley, D. E., Stevenson, R. W., Barrett, E. J., & Treadway, J. L. (1998). Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proceedings of the National Academy of Sciences of the United States of America, 95(4), 1776-1781. https://doi.org/10.1073/pnas.95.4.1776

Marx, B., Scuvee, E., Scuvee-Moreau, J., Seutin, V., & Jouret, F. (2016). Mechanisms of caffeine-induced diuresis. Medical Science (Paris), 32(5), 485-490. https://doi.org/10.1051/medsci/20163205015

Matsuoka, S., Ballif, B. A., Smogorzewska, A., McDonald, E. R., 3rd, Hurov, K. E., Luo, J., Bakalarski, C. E., Zhao, Z., Solimini, N., Lerenthal, Y., Shiloh, Y., Gygi, S. P., & Elledge, S. J. (2007). ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science, 316(5828), 1160-1166. https://doi.org/10.1126/science.1140321

Mattila, M. J., Palva, E., & Savolainen, K. (1982). Caffeine antagonizes diazepam effects in man. Medical Biology, 60(2), 121-123.

May, D. C., Jarboe, C. H., VanBakel, A. B., & Williams, W. M. (1982). Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clinical Pharmacology & Therapeutics, 31(5), 656-661. https://doi.org/10.1038/clpt.1982.91

Mazziotta, C., Rotondo, J. C., Lanzillotti, C., Campione, G., Martini, F., & Tognon, M. (2022). Cancer biology and molecular genetics of a(3) adenosine receptor. Oncogene, 41(3), 301-308. https://doi.org/10.1038/s41388-021-02090-z

Mazzotti, D. R., Guindalini, C., Pellegrino, R., Barrueco, K. F., Santos-Silva, R., Bittencourt, L. R., & Tufik, S. (2011). Effects of the adenosine deaminase polymorphism and caffeine intake on sleep parameters in a large population sample. Sleep, 34(3), 399-402. https://doi.org/10.1093/sleep/34.3.399

McPhersonx, P. S., Kim, Y. K., Valdivia, H., Knudson, C. M., Takekura, H., Franzini-Armstrong, C., Coronadot, R., & Campbell, K. P. (1991). The brain ryanodine receptor - A caffeine-sensitive calcium Release Channel. Neuron, 7(1), 17-25. https://doi.org/10.1016/0896-6273(91)90070-G

Mehta, A., & Patel, B. M. (2019). Therapeutic opportunities in colon cancer: Focus on phosphodiesterase inhibitors. Life Sciences, 230, 150-161. https://doi.org/10.1016/j.lfs.2019.05.043

Meisaprow, P., Aksorn, N., Vinayanuwattikun, C., Chanvorachote, P., & Sukprasansap, M. (2021). Caffeine induces G0/G1 cell cycle arrest and inhibits migration through integrin alpha v, beta 3, and FAK/Akt/c-Myc Signaling pathway. Molecules, 26(24), 7659. https://doi.org/10.3390/molecules26247659

Meissner, G. (1994). Ryanodine receptor Ca2+ release channels and their regulation by endogenous effectors. Annual Review of Physiology, 56, 485-508. https://doi.org/10.1146/annurev.ph.56.030194.002413

Merighi, S., Benini, A., Mirandola, P., Gessi, S., Varani, K., Simioni, C., Leung, E., Maclennan, S., Baraldi, P. G., & Borea, P. A. (2007). Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1α, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells. Molecular Pharmacology, 72(2), 395-406.

Merola, A., Germuska, M. A., Warnert, E. A., Richmond, L., Helme, D., Khot, S., Murphy, K., Rogers, P. J., Hall, J. E., & Wise, R. G. (2017). Mapping the pharmacological modulation of brain oxygen metabolism: The effects of caffeine on absolute CMRO2 measured using dual calibrated fMRI. NeuroImage, 155, 331-343. https://doi.org/10.1016/j.neuroimage.2017.03.028

Michelangeli, F., Mezna, M., Tovey, S., & Sayers, L. G. (1995). Pharmacological modulators of the inositol 1,4,5-trisphosphate receptor. Neuropharmacology, 34(9), 1111-1122. https://doi.org/10.1016/0028-3908(95)00053-9

Micioni di Bonaventura, M. V., Pucci, M., Giusepponi, M. E., Romano, A., Lambertucci, C., Volpini, R., Micioni di Bonaventura, E., Gaetani, S., Maccarrone, M., D'Addario, C., & Cifani, C. (2019). Regulation of adenosine A(2A) receptor gene expression in a model of binge eating in the amygdaloid complex of female rats. Journal of Psychopharmacology, 33(12), 1550-1561. https://doi.org/10.1177/0269881119845798

Milanez, S. (2011). Adverse health effects of caffeine: Review and analysis of recent human and animal research. USA Food and Drug Administration. Oak Ridge National Laboratory.

Miller, P. E., Zhao, D., Frazier-Wood, A. C., Michos, E. D., Averill, M., Sandfort, V., Burke, G. L., Polak, J. F., Lima, J. A. C., Post, W. S., Blumenthal, R. S., Guallar, E., & Martin, S. S. (2017). Associations of coffee, tea, and caffeine intake with coronary artery calcification and cardiovascular events. The American Journal of Medicine, 130(2), 188-197.e5.

Miners, J. O., & Birkett, D. J. (1996). The use of caffeine as a metabolic probe for human drug metabolizing enzymes. General Pharmacology-the Vascular System, 27(2), 245-249. https://doi.org/10.1016/0306-3623(95)02014-4

Miwa, S., Sugimoto, N., Shirai, T., Hayashi, K., Nishida, H., Ohnari, I., Takeuchi, A., Yachie, A., & Tsuchiya, H. (2011). Caffeine activates tumor suppressor PTEN in sarcoma cells. International Journal of Oncology, 39(2), 465-472. https://doi.org/10.3892/ijo.2011.1051

Miwa, S., Sugimoto, N., Yamamoto, N., Shirai, T., Nishida, H., Hayashi, K., Kimura, H., Takeuchi, A., Igarashi, K., Yachie, A., & Tsuchiya, H. (2012). Caffeine induces apoptosis of osteosarcoma cells by inhibiting AKT/mTOR/S6K. ANTICANCER RES, 32(9), 3643-3649.

Mizrak, D., Bayin, N. S., Yuan, J., Liu, Z., Suciu, R. M., Niphakis, M. J., Ngo, N., Lum, K. M., Cravatt, B. F., Joyner, A. L., & Sims, P. A. (2020). Single-cell profiling and SCOPE-Seq reveal lineage dynamics of adult ventricular-subventricular zone neurogenesis and NOTUM as a key regulator. Cell Reports, 31(12), 107805.

Modi, A. A., Feld, J. J., Park, Y., Kleiner, D. E., Everhart, J. E., Liang, T. J., & Hoofnagle, J. H. (2010). Increased caffeine consumption is associated with reduced hepatic fibrosis. Hepatology, 51(1), 201-209. https://doi.org/10.1002/hep.23279

Moschino, L., Zivanovic, S., Hartley, C., Trevisanuto, D., Baraldi, E., & Roehr, C. C. (2020). Caffeine in preterm infants: Where are we in 2020? Erj Open Research, 6(1), 330. https://doi.org/10.1183/23120541.00330-2019

Mumford, G. K., Benowitz, N. L., Evans, S. M., Kaminski, B. J., Preston, K. L., Sannerud, C. A., Silverman, K., & Griffiths, R. R. (1996). Absorption rate of methylxanthines following capsules, cola and chocolate. European Journal of Clinical Pharmacology, 51(3-4), 319-325. https://doi.org/10.1007/s002280050205

Mumin, A., Akhter, K., Abedin, M., & Hossain, Z. (2006). Determination and characterization of caffeine in tea, coffee and soft drinks by solid phase extraction and high performance liquid chromatography (SPE - HPLC). Malaysian Journal of Chemistry, 8, 45-51.

Musgrave, I. F., Farrington, R. L., Hoban, C., & Byard, R. W. (2016). Caffeine toxicity in forensic practice: Possible effects and under-appreciated sources. Forensic Science, Medicine, and Pathology, 12(3), 299-303. https://doi.org/10.1007/s12024-016-9786-9

Mustafa, S. J., Morrison, R. R., Teng, B., & Pelleg, A. (2009). Adenosine receptors and the heart: Role in regulation of coronary blood flow and cardiac electrophysiology. In S. Mustafa & C. Wilson (Eds.), Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology (Vol. 193) Springer.

Mustard, J. A. (2014). The buzz on caffeine in invertebrates: Effects on behavior and molecular mechanisms. Cellular and Molecular Life Sciences, 71(8), 1375-1382. https://doi.org/10.1007/s00018-013-1497-8

Nabbi-Schroeter, D., Elmenhorst, D., Oskamp, A., Laskowski, S., Bauer, A., & Kroll, T. (2018). Effects of long-term caffeine consumption on the adenosine A1 receptor in the rat brain: An In vivo PET study with [(18)F]CPFPX. Molecular Imaging and Biology, 20(2), 284-291. https://doi.org/10.1007/s11307-017-1116-4

Nakaso, K., Ito, S., & Nakashima, K. (2008). Caffeine activates the PI3K/Akt pathway and prevents apoptotic cell death in a Parkinson's disease model of SH-SY5Y cells. Neuroscience Letters, 432(2), 146-150. https://doi.org/10.1016/j.neulet.2007.12.034

Nardi, A. E., Lopes, F. L., Freire, R. C., Veras, A. B., Nascimento, I., Valenca, A. M., de Melo-Neto, V. L., Soares-Filho, G. L., King, A. L., Araújo, D. M., Mezzasalma, M. A., Rassi, A., & Zin, W. A. (2009). Panic disorder and social anxiety disorder subtypes in a caffeine challenge test. Psychiatry Research, 169(2), 149-153. https://doi.org/10.1016/j.psychres.2008.06.023

Nawrot, P., Jordan, S., Eastwood, J., Rotstein, J., Hugenholtz, A., & Feeley, M. (2003). Effects of caffeine on human health. Food Additives and Contaminants, 20(1), 1-30. https://doi.org/10.1080/0265203021000007840

Nehlig, A. (2010). Is caffeine a cognitive enhancer? Journal of Alzheimers Disease, 20, S85-S94. https://doi.org/10.3233/Jad-2010-091315

Nehlig, A. (2018). Interindividual differences in caffeine metabolism and factors driving caffeine consumption. Pharmacological Reviews, 70(2), 384-411. https://doi.org/10.1124/pr.117.014407

Nehlig, A., Daval, J. L., Pereira de Vasconcelos, A., & Boyet, S. (1987). Caffeine-diazepam interaction and local cerebral glucose utilization in the conscious rat. Brain Research, 419(1-2), 272-278. https://doi.org/10.1016/0006-8993(87)90593-2

Newgard, C. B., Hwang, P. K., & Fletterick, R. J. (1989). The family of glycogen phosphorylases: Structure and functio. Critical Reviews in Biochemistry and Molecular Biology, 24(1), 69-99.

Nicholson, K. M., & Anderson, N. G. (2002). The protein kinase B/Akt signalling pathway in human malignancy. Cellular Signalling, 14(5), 381-395. https://doi.org/10.1016/S0898-6568(01)00271-6

Nilnumkhum, A., Kanlaya, R., Yoodee, S., & Thongboonkerd, V. (2019). Caffeine inhibits hypoxia-induced renal fibroblast activation by antioxidant mechanism. Cell Adhesion & Migration, 13(1), 260-272. https://doi.org/10.1080/19336918.2019.1638691

Nkondjock, A. (2009). Coffee consumption and the risk of cancer: An overview. Cancer Letters, 277(2), 121-125. https://doi.org/10.1016/j.canlet.2008.08.022

Nunes, R. A., Mazzotti, D. R., Hirotsu, C., Andersen, M. L., Tufik, S., & Bittencourt, L. (2017). The association between caffeine consumption and objective sleep variables is dependent on ADORA2A c.1083T>C genotypes. Sleep Medicine, 30, 210-215. https://doi.org/10.1016/j.sleep.2016.06.038

Oberleitner, L., Grandke, J., Mallwitz, F., Resch-Genger, U., Garbe, L.-A., & Schneider, R. J. (2014). Fluorescence polarization immunoassays for the quantification of caffeine in beverages. Journal of Agricultural and Food Chemistry, 62(11), 2337-2343.

O'Driscoll, M., Ruiz-Perez, V. L., Woods, C. G., Jeggo, P. A., & Goodship, J. A. (2003). A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nature Genetics, 33(4), 497-501. https://doi.org/10.1038/ng1129

Ogawa, Y. (1994). Role of ryanodine receptors. Critical Reviews in Biochemistry and Molecular Biology, 29(4), 229-274. https://doi.org/10.3109/10409239409083482

Ohta, A., Gorelik, E., Prasad, S. J., Ronchese, F., Lukashev, D., Wong, M. K., Huang, X., Caldwell, S., Liu, K., Smith, P., Chen, J. F., Jackson, E. K., Apasov, S., Abrams, S., & Sitkovsky, M. (2006). A2A adenosine receptor protects tumors from antitumor T cells. Proceedings of the National Academy of Sciences of the United States of America, 103(35), 13132-13137. https://doi.org/10.1073/pnas.0605251103

Oikonomakos, N. G. (2002). Glycogen phosphorylase as a molecular target for type 2 diabetes therapy. Current Protein & Peptide Science, 3(6), 561-586. https://doi.org/10.2174/1389203023380422

Oikonomakos, N. G., Schnier, J. B., Zographos, S. E., Skamnaki, V. T., Tsitsanou, K. E., & Johnson, L. N. (2000). Flavopiridol inhibits glycogen phosphorylase by binding at the inhibitor site. Journal of Biological Chemistry, 275(44), 34566-34573. https://doi.org/10.1074/jbc.M004485200

Okano, J., Nagahara, T., Matsumoto, K., & Murawaki, Y. (2008). Caffeine inhibits the proliferation of liver cancer cells and activates the MEK/ERK/EGFR signalling pathway. Basic & Clinical Pharmacology & Toxicology, 102(6), 543-551. https://doi.org/10.1111/j.1742-7843.2008.00231.x

O'Keefe, J. H., Bhatti, S. K., Patil, H. R., DiNicolantonio, J. J., Lucan, S. C., & Lavie, C. J. (2013). Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality. Journal of the American College of Cardiology, 62(12), 1043-1051.

Oliveira Kda, S., Buss, C., & Tovo, C. V. (2015). Association of caffeine intake and liver fibrosis in patients with chronic hepatitis C. Arquivos de Gastroenterologia, 52(1), 4-8. https://doi.org/10.1590/S0004-28032015000100002

Orban, C., Vasarhelyi, Z., Bajnok, A., Sava, F., & Toldi, G. (2018). Effects of caffeine and phosphodiesterase inhibitors on activation of neonatal T lymphocytes. Immunobiology, 223(11), 627-633. https://doi.org/10.1016/j.imbio.2018.07.008

Osaki, M., Oshimura, M., & Ito, H. (2004). PI3K-Akt pathway: Its functions and alterations in human cancer. Apoptosis, 9(6), 667-676. https://doi.org/10.1023/B:APPT.0000045801.15585.dd

Othman, M. A., Fadel, R., Tayem, Y., Jaradat, A., Rashid, A., Fatima, A., al-Mahameed, A. E., & Nasr el-Din, W. A. (2023). Caffeine protects against hippocampal alterations in type 2 diabetic rats via modulation of gliosis, inflammation and apoptosis. Cell and Tissue Research, 392(2), 443-466. https://doi.org/10.1007/s00441-022-03735-5

Ozawa, T. (2010). Modulation of ryanodine receptor Ca2+ channels (review). Molecular Medicine Reports, 3(2), 199-204. https://doi.org/10.3892/mmr_00000240

Page, C., Schudt, C., Dent, G., & Rabe, K. F. (1996). Phosphodiesterase inhibitors. Elsevier.

Park, C. A., Kang, C. K., Son, Y. D., Choi, E. J., Kim, S. H., Oh, S. T., Kim, Y. B., Park, C. W., & Cho, Z. H. (2014). The effects of caffeine ingestion on cortical areas: Functional imaging study. Magnetic Resonance Imaging, 32(4), 366-371. https://doi.org/10.1016/j.mri.2013.12.018

Passmore, A. P., Kondowe, G. B., & Johnston, G. D. (1987). Renal and cardiovascular effects of caffeine: A dose-response study. Clinical Science (London, England), 72(6), 749-756. https://doi.org/10.1042/cs0720749

Paull, T. T. (2015). Mechanisms of ATM activation. Annual Review of Biochemistry, 84, 711-738. https://doi.org/10.1146/annurev-biochem-060614-034335

Pauwels, E. K. J., & Volterrani, D. (2021). Coffee consumption and cancer risk: An assessment of the health implications based on recent knowledge. Medical Principles and Practice, 30(5), 401-411. https://doi.org/10.1159/000516067

Peerapen, P., Ausakunpipat, N., Sutthimethakorn, S., Aluksanasuwan, S., Vinaiphat, A., & Thongboonkerd, V. (2017). Physiologic changes of urinary proteome by caffeine and excessive water intake. Clinical Chemistry and Laboratory Medicine, 55(7), 993-1002. https://doi.org/10.1515/cclm-2016-0464

Peerapen, P., & Thongboonkerd, V. (2016). Caffeine prevents kidney stone formation by translocation of apical surface annexin A1 crystal-binding protein into cytoplasm: In vitro evidence. Scientific Reports, 6, 38536. https://doi.org/10.1038/srep38536

Peerapen, P., & Thongboonkerd, V. (2018). Caffeine in Kidney Stone Disease: Risk or Benefit? Advances in Nutrition, 9(4), 419-424. https://doi.org/10.1093/advances/nmy016

Pelchovitz, D. J., & Goldberger, J. J. (2011). Caffeine and cardiac arrhythmias: A review of the evidence. The American Journal of Medicine, 124(4), 284-289. https://doi.org/10.1016/j.amjmed.2010.10.017

Peng, W., Shen, H., Wu, J., Guo, W., Pan, X., Wang, R., Chen, S. R. W., & Yan, N. (2016). Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2. Science, 354(6310), aah5324. https://doi.org/10.1126/science.aah5324

Peng, Z., Fernandez, P., Wilder, T., Yee, H., Chiriboga, L., Chan, E. S., & Cronstein, B. N. (2008). Ecto-5′-nucleotidase (CD73)-mediated extracellular adenosine production plays a critical role in hepatic fibrosis. FASEB Journal, 22(7), 2263-2272. https://doi.org/10.1096/fj.07-100685

Pentinmikko, N., Iqbal, S., Mana, M., Andersson, S., Cognetta, A. B., Suciu, R. M., Roper, J., Luopajärvi, K., Markelin, E., Gopalakrishnan, S., Smolander, O. P., Naranjo, S., Saarinen, T., Juuti, A., Pietiläinen, K., Auvinen, P., Ristimäki, A., Gupta, N., Tammela, T., … Katajisto, P. (2019). Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium. Nature, 571(7765), 398-402.

Persson, C. G., Karlsson, J. A., & Erjefält, I. (1982). Differentiation between bronchodilation and universal adenosine antagonism among xanthine derivatives. Life Sciences, 30(25), 2181-2189. https://doi.org/10.1016/0024-3205(82)90292-2

Pohanka, M. (2011). Cholinesterases, a target of pharmacology and toxicology. Biomedical Papers of the Medical Faculty of Palacky University in Olomouc, 155(3), 219-229.

Pohanka, M. (2012). Acetylcholinesterase inhibitors: A patent review (2008-present). Expert Opinion on Therapeutic Patents, 22(8), 871-886.

Pohanka, M. (2022). Role of caffeine in the age-related neurodegenerative diseases: A review. Mini Reviews in Medicinal Chemistry, 22(21), 2726-2735. https://doi.org/10.2174/1389557522666220413103529

Pohanka, M., & Dobes, P. (2013). Caffeine inhibits acetylcholinesterase, but not butyrylcholinesterase. International Journal of Molecular Sciences, 14(5), 9873-9882.

Porta, M., Zima, A. V., Nani, A., Diaz-Sylvester, P. L., Copello, J. A., Ramos-Franco, J., Blatter, L. A., & Fill, M. (2011). Single ryanodine receptor channel basis of caffeine's action on Ca2+ sparks. Biophysical Journal, 100(4), 931-938. https://doi.org/10.1016/j.bpj.2011.01.017

Pounis, G., Tabolacci, C., Costanzo, S., Cordella, M., Bonaccio, M., Rago, L., D'Arcangelo, D., Filippo di Castelnuovo, A., de Gaetano, G., Donati, M. B., Iacoviello, L., Facchiano, F., & Moli-sani study investigators. (2017). Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli-sani cohort and cellular models. International Journal of Cancer, 141(1), 72-82. https://doi.org/10.1002/ijc.30720

Prinz, G., & Diener, M. (2008). Characterization of ryanodine receptors in rat colonic epithelium. Acta Physiologica (Oxford, England), 193(2), 151-162. https://doi.org/10.1111/j.1748-1716.2007.01802.x

Qian, J., Chen, Q., Ward, S. M., Duan, E., & Zhang, Y. (2020). Impacts of caffeine during pregnancy. Trends in Endocrinology and Metabolism, 31(3), 218-227. https://doi.org/10.1016/j.tem.2019.11.004

Ralevic, V., & Dunn, W. R. (2015). Purinergic transmission in blood vessels. Autonomic Neuroscience, 191, 48-66. https://doi.org/10.1016/j.autneu.2015.04.007

Ramamoorthy, V., Campa, A., Rubens, M., Martinez, S. S., Fleetwood, C., Stewart, T., Liuzzi, J. P., George, F., Khan, H., Li, Y., & Baum, M. K. (2017). The relationship between caffeine intake and immunological and Virological markers of HIV disease progression in Miami adult studies on HIV cohort. Viral Immunology, 30(4), 271-277. https://doi.org/10.1089/vim.2016.0148

Ramkumar, V., Bumgarner, J. R., Jacobson, K. A., & Stiles, G. L. (1988). Multiple components of the A1 adenosine receptor-adenylate cyclase system are regulated in rat cerebral cortex by chronic caffeine ingestion. The Journal of Clinical Investigation, 82(1), 242-247. https://doi.org/10.1172/JCI113577

Ran, H. Q., Wang, J. Z., & Sun, C. Q. (2016). Coffee consumption and pancreatic cancer risk: An update meta-analysis of cohort studies. Pak J Med Sci, 32(1), 253-259. https://doi.org/10.12669/pjms.321.8761

Rath, V., Ammirati, M., Danley, D., Ekstrom, J., Gibbs, E., Hynes, T., Mathiowetz, A. M., McPherson, R. K., Olson, T. V., Treadway, J. L., & Hoover, D. J. (2000). Human liver glycogen phosphorylase inhibitors bind at a new allosteric site. Chemistry & Biology, 7, 677-682. https://doi.org/10.1016/S1074-5521(00)00004-1

Reichert, C. F., Deboer, T., & Landolt, H. P. (2022). Adenosine, caffeine, and sleep-wake regulation: State of the science and perspectives. Journal of Sleep Research, 31(4), e13597. https://doi.org/10.1111/jsr.13597

Retey, J. V., Adam, M., Gottselig, J. M., Khatami, R., Durr, R., Achermann, P., & Landolt, H. P. (2006). Adenosinergic mechanisms contribute to individual differences in sleep deprivation-induced changes in neurobehavioral function and brain rhythmic activity. Journal of Neuroscience, 26(41), 10472-10479. https://doi.org/10.1523/Jneurosci.1538-06.2006

Rétey, J. V., Adam, M., Honegger, E., Khatami, R., Luhmann, U. F. O., Jung, H. H., Berger, W., & Landolt, H. P. (2005). A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proceedings of the National Academy of Sciences of the United States of America, 102(43), 15676-15681. https://doi.org/10.1073/pnas.0505414102

Retey, J. V., Adam, M., Khatami, R., Luhmann, U. F., Jung, H. H., Berger, W., & Landolt, H. P. (2007). A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clinical Pharmacology & Therapeutics, 81(5), 692-698. https://doi.org/10.1038/sj.clpt.6100102

Richards, G., & Smith, A. (2015). Caffeine consumption and self-assessed stress, anxiety, and depression in secondary school children. Journal of Psychopharmacology, 29(12), 1236-1247. https://doi.org/10.1177/0269881115612404

Ritchie, K., Carriere, I., de Mendonca, A., Portet, F., Dartigues, J. F., Rouaud, O., Barberger-Gateau, P., & Ancelin, M. L. (2007). The neuroprotective effects of caffeine: A prospective population study (the three City study). Neurology, 69(6), 536-545. https://doi.org/10.1212/01.wnl.0000266670.35219.0c

Ritter, M., Hohenberger, K., Alter, P., Herzum, M., Tebbe, J., & Maisch, M. (2005). Caffeine inhibits cytokine expression in lymphocytes. Cytokine, 30(4), 177-181. https://doi.org/10.1016/j.cyto.2004.12.013

Rivera-Oliver, M., & Diaz-Rios, M. (2014). Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: A review. Life Sciences, 101(1-2), 1-9. https://doi.org/10.1016/j.lfs.2014.01.083

Rivkees, S. A., & Wendler, C. C. (2011). Adverse and protective influences of adenosine on the Newborn and embryo: Implications for preterm White matter injury and embryo protection. Pediatric Research, 69(4), 271-278. https://doi.org/10.1203/PDR.0b013e31820efbcf

Rocha, S., Lucas, M., Araújo, A. N., Corvo, M. L., Fernandes, E., & Freitas, M. (2021). Optimization and validation of an in vitro standardized glycogen phosphorylase activity assay. Molecules, 26(15), 4635.

Rodak, K., Kokot, I., & Kratz, E. M. (2021). Caffeine as a factor influencing the functioning of the human body-Friend or foe? Nutrients, 13(9), 3088. https://doi.org/10.3390/nu13093088

Rohrig, T., Liesenfeld, D., & Richling, E. (2017). Identification of a Phosphodiesterase-inhibiting fraction from roasted coffee (Coffea arabica) through activity-guided fractionation. Journal of Agricultural and Food Chemistry, 65(19), 3792-3800. https://doi.org/10.1021/acsjafc.6b05613

Romero-Martínez, B. S., Montaño, L. M., Solís-Chagoyán, H., Sommer, B., Ramírez-Salinas, G. L., Pérez-Figueroa, G. E., & Flores-Soto, E. (2021). Possible beneficial actions of caffeine in SARS-CoV-2. International Journal of Molecular Sciences, 22(11), 5460. https://doi.org/10.3390/ijms22115460

Rosendahl, A. H., Perks, C. M., Zeng, L., Markkula, A., Simonsson, M., Rose, C., Ingvar, C., Holly, J. M. P., & Jernström, H. (2015). Caffeine and Caffeic acid inhibit growth and modify Estrogen receptor and insulin-like growth factor I receptor levels in human breast cancer. Clinical Cancer Research, 21(8), 1877-1887. https://doi.org/10.1158/1078-0432.CCR-14-1748

Roskoski, R. (2021). Properties of FDA-approved small molecule phosphatidylinositol 3-kinase inhibitors prescribed for the treatment of malignancies. Pharmacological Research, 168, 105579. https://doi.org/10.1016/j.phrs.2021.105579

Rossi, R., Bottinelli, R., Sorrentino, V., & Reggiani, C. (2001). Response to caffeine and ryanodine receptor isoforms in mouse skeletal muscles. American Journal of Physiology-Cell Physiology, 281(2), C585-C594.

Rowley, R. (1992). Reduction of radiation-induced G2 arrest by caffeine. Radiation Research, 129(2), 224-227. https://doi.org/10.2307/3578161

Rudolph, T., & Knudsen, K. (2010). A case of fatal caffeine poisoning. Acta Anaesthesiologica Scandinavica, 54(4), 521-523. https://doi.org/10.1111/j.1399-6576.2009.02201.x

Rudolph, U., Crestani, F., Benke, D., Brünig, I., Benson, J. A., Fritschy, J. M., Martin, J. R., Bluethmann, H., & Möhler, H. (1999). Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes. Nature, 401(6755), 796-800. https://doi.org/10.1038/44579

Ruhl, C. E., & Everhart, J. E. (2005). Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology, 128(1), 24-32. https://doi.org/10.1053/j.gastro.2004.09.075

Sachse, C., Brockmoller, J., Bauer, S., & Roots, I. (1999). Functional significance of a C-->a polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. British Journal of Clinical Pharmacology, 47(4), 445-449. https://doi.org/10.1046/j.1365-2125.1999.00898.x

Saiki, S., Sasazawa, Y., Imamichi, Y., Kawajiri, S., Fujimaki, T., Tanida, I., Kobayashi, H., Sato, F., Sato, S., Ishikawa, K., Imoto, M., & Hattori, N. (2011). Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy, 7(2), 176-187. https://doi.org/10.4161/auto.7.2.14074

Saleem, H., Tovey, S. C., Molinski, T. F., & Taylor, C. W. (2014). Interactions of antagonists with subtypes of inositol 1,4,5-trisphosphate (IP3) receptor. British Journal of Pharmacology, 171(13), 3298-3312. https://doi.org/10.1111/bph.12685

Samieirad, S., Afrasiabi, H., Tohidi, E., Qolizade, M., Shaban, B., Hashemipour, M. A., & Doaltian Shirvan, I. (2017). Evaluation of caffeine versus codeine for pain and swelling management after implant surgeries: A triple blind clinical trial. Journal of Cranio-Maxillo-Facial Surgery, 45(10), 1614-1621. https://doi.org/10.1016/j.jcms.2017.06.014

Sansone, R., Ottaviani, J. I., Rodriguez-Mateos, A., Heinen, Y., Noske, D., Spencer, J. P., Crozier, A., Merx, M. W., Kelm, M., Schroeter, H., & Heiss, C. (2017). Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: Randomized, double-masked controlled studies. The American Journal of Clinical Nutrition, 105(2), 352-360. https://doi.org/10.3945/ajcn.116.140046

Sarkaria, J. N., Busby, E. C., Tibbetts, R. S., Roos, P., Taya, Y., Karnitz, L. M., & Abraham, R. T. (1999). Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Research, 59(17), 4375-4382.

Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D. A., Smith, S., Uziel, T., Sfez, S., Ashkenazi, M., Pecker, I., Frydman, M., Harnik, R., Patanjali, S. R., Simmons, A., Clines, G. A., Sartiel, A., Gatti, R. A., … Shiloh, Y. (1995). A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science, 268(5218), 1749-1753. https://doi.org/10.1126/science.7792600

Sawynok, J. (2011). Caffeine and pain. Pain, 152(4), 726-729.

Sawynok, J., & Yaksh, T. L. (1993). Caffeine as an analgesic adjuvant - A review of pharmacology and mechanisms of action. Pharmacological Reviews, 45(1), 43-85.

Schlegel, R., & Pardee, A. B. (1986). Caffeine-induced uncoupling of mitosis from the completion of DNA replication in mammalian cells. Science, 232(4755), 1264-1266. https://doi.org/10.1126/science.2422760

Schubert, M. M., Hall, S., Leveritt, M., Grant, G., Sabapathy, S., & Desbrow, B. (2014). Caffeine consumption around an exercise bout: Effects on energy expenditure, energy intake, and exercise enjoyment. Journal of Applied Physiology (Bethesda, MD: 1985), 117(7), 745-754. https://doi.org/10.1152/japplphysiol.00570.2014

Sesso, H. D., Gaziano, J. M., Buring, J. E., & Hennekens, C. H. (1999). Coffee and tea intake and the risk of myocardial infarction. American Journal of Epidemiology, 149(2), 162-167. https://doi.org/10.1093/oxfordjournals.aje.a009782

Shan, L., Wang, F., Zhai, D., Meng, X., Liu, J., & Lv, X. (2022). Caffeine in liver diseases. Pharmacology and Toxicology, 13, 1030173. https://doi.org/10.3389/fphar.2022.1030173

Sharif, K., Watad, A., Bragazzi, N. L., Adawi, M., Amital, H., & Shoenfeld, Y. (2017). Coffee and autoimmunity: More than a mere hot beverage! Autoimmunity Reviews, 16(7), 712-721. https://doi.org/10.1016/j.autrev.2017.05.007

Sharma, D., & Bansal, A. (2020). The bitter the taste, the better is the medicine: Is caffeine the answer to COVID-19? AIJR Preprints, 78(1), 1-3.

Sharmin, S., Guan, H., Williams, A. S., & Yang, K. (2012). Caffeine reduces 11β-hydroxysteroid dehydrogenase type 2 expression in human trophoblast cells through the adenosine A2B receptor. PLoS One, 7(6), e38082.

Shaw, R. J., & Cantley, L. C. (2006). Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature, 441(7092), 424-430. https://doi.org/10.1038/nature04869

Shen, H. F., Rodriguez, A. C., Shiani, A., Lipka, S., Shahzad, G., Kumar, A., & Mustacchia, P. (2016). Association between caffeine consumption and nonalcoholic fatty liver disease: A systemic review and meta-analysis. Therapeutic Advances in Gastroenterology, 9(1), 113-120. https://doi.org/10.1177/1756283x15593700

Shi, D., Nikodijevic, O., Jacobson, K. A., & Daly, J. W. (1993). Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain. Cellular and Molecular Neurobiology, 13(3), 247-261. https://doi.org/10.1007/BF00733753

Shi, D., Padgett, W. L., & Daly, J. W. (2003). Caffeine analogs: Effects on ryanodine-sensitive calcium-release channels and GABA a receptors. Cellular and Molecular Neurobiology, 23(3), 331-347.

Shiloh, Y., & Ziv, Y. (2013). The ATM protein kinase: Regulating the cellular response to genotoxic stress, and more. Nature Reviews. Molecular Cell Biology, 14(4), 197-210.

Shim, S. G., Jun, D. W., Kim, E. K., Saeed, W. K., Lee, K. N., Lee, H. L., Lee, O. Y., Choi, H. S., & Yoon, B. C. (2013). Caffeine attenuates liver fibrosis via defective adhesion of hepatic stellate cells in cirrhotic model. Journal of Gastroenterology and Hepatology, 28(12), 1877-1884. https://doi.org/10.1111/jgh.12317

Shirley, D. G., Walter, S. J., & Noormohamed, F. H. (2002). Natriuretic effect of caffeine: Assessment of segmental sodium reabsorption in humans. Clinical Science (London, England), 103(5), 461-466. https://doi.org/10.1042/cs1030461

Shrestha, B., & Jawa, G. (2017). Caffeine citrate - Is it a silver bullet in neonatology? Pediatrics and Neonatology, 58(5), 391-397. https://doi.org/10.1016/j.pedneo.2016.10.003

Sieghart, W. (1994). Pharmacology of benzodiazepine receptors: An update. Journal of Psychiatry & Neuroscience, 19(1), 24-29.

Silman, I., & Sussman, J. L. (2005). Acetylcholinesterase: ‘Classical’ and ‘non-classical' functions and pharmacology. Current Opinion in Pharmacology, 5(3), 293-302. https://doi.org/10.1016/j.coph.2005.01.014

Simonin, C., Duru, C., Salleron, J., Hincker, P., Charles, P., Delval, A., Youssov, K., Burnouf, S., Azulay, J. P., Verny, C., Scherer, C., Tranchant, C., Goizet, C., Debruxelles, S., Defebvre, L., Sablonnière, B., Romon-Rousseaux, M., Buée, L., Destée, A., … Huntington French Speaking Network. (2013). Association between caffeine intake and age at onset in Huntington's disease. Neurobiology of Disease, 58, 179-182. https://doi.org/10.1016/j.nbd.2013.05.013

Sinha, R. A., Farah, B. L., Singh, B. K., Siddique, M. M., Li, Y., Wu, Y., Ilkayeva, O. R., Gooding, J., Ching, J., Zhou, J., Martinez, L., Xie, S., Bay, B. H., Summers, S. A., Newgard, C. B., & Yen, P. M. (2014). Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice. Hepatology, 59(4), 1366-1380. https://doi.org/10.1002/hep.26667

Skarupke, C., Schlack, R., Lange, K., Goerke, M., Dueck, A., Thome, J., Szagun, B., & Cohrs, S. (2017). Insomnia complaints and substance use in German adolescents: Did we underestimate the role of coffee consumption? Results of the KiGGS study. Journal of Neural Transmission (Vienna), 124(Suppl 1), 69-78. https://doi.org/10.1007/s00702-015-1448-7

Slomovitz, B. M., & Coleman, R. L. (2012). The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clinical Cancer Research, 18(21), 5856-5864. https://doi.org/10.1158/1078-0432.Ccr-12-0662

Smith, A. (2002). Effects of caffeine on human behavior. Food and Chemical Toxicology, 40(9), 1243-1255. https://doi.org/10.1016/s0278-6915(02)00096-0

Smith, A., Brice, C., Nash, J., Rich, N., & Nutt, D. J. (2003). Caffeine and central noradrenaline: Effects on mood, cognitive performance, eye movements and cardiovascular function. Journal of Psychopharmacology, 17(3), 283-292. https://doi.org/10.1177/02698811030173010

Smith, G. C. M., & Jackson, S. P. (2003). Handbook of cell signaling. Elsevier Academic Press: New York, 1, 557-561.

Snel, J., & Lorist, M. M. (2011). Chapter 6 - Effects of caffeine on sleep and cognition. In H. P. A. Van Dongen & G. A. Kerkhof (Eds.), Progress in brain research (Vol. 190, pp. 105-117). Elsevier.

Song, F. J., Qureshi, A. A., & Han, J. L. (2012). Increased caffeine intake is associated with reduced risk of basal cell carcinoma of the skin. Cancer Research, 72(13), 3282-3289. https://doi.org/10.1158/0008-5472.Can-11-3511

Spielman, W. S., & Arend, L. J. (1991). Adenosine receptors and signaling in the kidney. Hypertension, 17(2), 117-130. https://doi.org/10.1161/01.hyp.17.2.117

Sprang, S., Fletterick, R., Stern, M., Yang, D., Madsen, N., & Sturtevant, J. (1982). Analysis of an allosteric binding site: The nucleoside inhibitor site of phosphorylase alpha. Biochemistry, 21(9), 2036-2048. https://doi.org/10.1021/bi00538a010

Stockwell, J., Jakova, E., & Cayabyab, F. S. (2017). Adenosine A1 and A2A receptors in the brain: Current research and their role in Neurodegeneration. Molecules, 22(4), 676. https://doi.org/10.3390/molecules22040676

Stouth, D. W., Lebeau, P. F., & Austin, R. C. (2023). Repurposing two old friends to fight cancer: Caffeine and statins. Cancer Research, 83(13), 2091-2092. https://doi.org/10.1158/0008-5472.CAN-23-1066

Sulem, P., Gudbjartsson, D. F., Geller, F., Prokopenko, I., Feenstra, B., Aben, K. K. H., Franke, B., den Heijer, M., Kovacs, P., Stumvoll, M., Mägi, R., Yanek, L. R., Becker, L. C., Boyd, H. A., Stacey, S. N., Walters, G. B., Jonasdottir, A., Thorleifsson, G., Holm, H., … Stefansson, K. (2011). Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption. Human Molecular Genetics, 20(10), 2071-2077. https://doi.org/10.1093/hmg/ddr086

Sullivan, G. W., Luong, L. S., Carper, H. T., Barnes, R. C., & Mandell, G. L. (1995). Methylxanthines with adenosine alter TNF alpha-primed PMN activation. Immunopharmacology, 31(1), 19-29. https://doi.org/10.1016/0162-3109(95)00030-0

Tatler, A. L., Barnes, J., Habgood, A., Goodwin, A., McAnulty, R. J., & Jenkins, G. (2016). Caffeine inhibits TGFbeta activation in epithelial cells, interrupts fibroblast responses to TGFbeta, and reduces established fibrosis in ex vivo precision-cut lung slices. Thorax, 71(6), 565-567. https://doi.org/10.1136/thoraxjnl-2015-208215

Taylor, C. W., & Tovey, S. C. (2010). IP3 receptors: Toward understanding their activation. Cold Spring Harbor Perspectives in Biology, 2(12), a004010. https://doi.org/10.1101/cshperspect.a004010

Tej, G., & Nayak, P. K. (2018). Mechanistic considerations in chemotherapeutic activity of caffeine. Biomedicine & Pharmacotherapy, 105, 312-319. https://doi.org/10.1016/j.biopha.2018.05.144

Tej, G. N. V. C., Neogi, K., Verma, S. S., Gupta, S. C., & Nayak, P. K. (2019). Caffeine-enhanced anti-tumor immune response through decreased expression of PD1 on infiltrated cytotoxic T lymphocytes. European Journal of Pharmacology, 859, 172538. https://doi.org/10.1016/j.ejphar.2019.172538

Temido-Ferreira, M., Ferreira, D. G., Batalha, V. L., Marques-Morgado, I., Coelho, J. E., Pereira, P., Gomes, R., Pinto, A., Carvalho, S., Canas, P. M., Cuvelier, L., Buée-Scherrer, V., Faivre, E., Baqi, Y., Müller, C. E., Pimentel, J., Schiffmann, S. N., Buée, L., Bader, M., … Lopes, L. V. (2020). Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors. Molecular Psychiatry, 25(8), 1876-1900.

The International Agency for Research on Cancer (Author). (1991). Coffee, tea, mate, methylxanthines and methylglyoxal. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 27 February to 6 March 1990. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 51, 1-513.

Thomson, S. A., Banker, P., Bickett, D. M., Boucheron, J. A., Carter, H. L., Clancy, D. C., Cooper, J. P., Dickerson, S. H., Garrido, D. M., Nolte, R. T., Peat, A. J., Sheckler, L. R., Sparks, S. M., Tavares, F. X., Wang, L., Wang, T. Y., & Weiel, J. E. (2009). Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy. Bioorganic & Medicinal Chemistry Letters, 19(4), 1177-1182. https://doi.org/10.1016/j.bmcl.2008.12.085

Thorn, C. F., Aklillu, E., McDonagh, E. M., Klein, T. E., & Altman, R. B. (2012). PharmGKB summary: Caffeine pathway. Pharmacogenetics and Genomics, 22(5), 389-395. https://doi.org/10.1097/FPC.0b013e3283505d5e

Tian, D. D., Natesan, S., White, J. R., Jr., & Paine, M. F. (2019). Effects of common CYP1A2 genotypes and other key factors on Intraindividual variation in the caffeine metabolic ratio: An exploratory analysis. Clinical and Translational Science, 12(1), 39-46. https://doi.org/10.1111/cts.12598

Tichý, A., Vávrová, J., Pejchal, J., & Rezácová, M. (2010). Ataxia-telangiectasia mutated kinase (ATM) as a central regulator of radiation-induced DNA damage response. Acta Medica (Hradec Králové), 53(1), 13-17.

Toescu, E. C., O'Neill, S. C., Petersen, O. H., & Eisner, D. A. (1992). Caffeine inhibits the agonist-evoked cytosolic Ca2+ signal in mouse pancreatic acinar cells by blocking inositol trisphosphate production. The Journal of Biological Chemistry, 267(33), 23467-23470.

Tofovic, S. P., Branch, K. R., Oliver, R. D., Magee, W. D., & Jackson, E. K. (1991). Caffeine potentiates vasodilator-induced renin release. Journal of Pharmacology and Experimental Therapeutics, 256(3), 850-860.

Tommerdahl, K. L., Hu, E. A., Selvin, E., Steffen, L. M., Coresh, J., Grams, M. E., Bjornstad, P., Rebholz, C. M., & Parikh, C. R. (2022). Coffee consumption May mitigate the risk for acute kidney injury: Results from the atherosclerosis risk in communities study. Kidney Int Rep, 7(7), 1665-1672. https://doi.org/10.1016/j.ekir.2022.04.091

Trang, J. M., Blanchard, J., Conrad, K. A., & Harrison, G. G. (1985). Relationship between Total-body clearance of caffeine and urine flow-rate in elderly men. Biopharmaceutics & Drug Disposition, 6(1), 51-56. https://doi.org/10.1002/bdd.2510060107

Tseng, C. J., Kuan, C. J., Chu, H., & Tung, C. S. (1993). Effect of caffeine treatment on plasma renin activity and angiotensin I concentrations in rats on a low sodium diet. Life Sciences, 52(10), 883-890. https://doi.org/10.1016/0024-3205(93)90518-8

Turnbull, D., Rodricks, J. V., & Mariano, G. F. (2016). Neurobehavioral hazard identification and characterization for caffeine. Regulatory Toxicology and Pharmacology, 74, 81-92. https://doi.org/10.1016/j.yrtph.2015.12.002

Turnbull, D., Rodricks, J. V., Mariano, G. F., & Chowdhury, F. (2017). Caffeine and cardiovascular health. Regulatory Toxicology and Pharmacology, 89, 165-185. https://doi.org/10.1016/j.yrtph.2017.07.025

Um, C. Y., McCullough, M. L., Guinter, M. A., Campbell, P. T., Jacobs, E. J., & Gapstur, S. M. (2020). Coffee consumption and risk of colorectal cancer in the cancer prevention study-II nutrition cohort. Cancer Epidemiology, 67, 101730. https://doi.org/10.1016/j.canep.2020.101730

Umemura, T., Ueda, K., Nishioka, K., Hidaka, T., Takemoto, H., Nakamura, S., Jitsuiki, D., Soga, J., Goto, C., Chayama, K., Yoshizumi, M., & Higashi, Y. (2006). Effects of acute administration of caffeine on vascular function. The American Journal of Cardiology, 98(11), 1538-1541. https://doi.org/10.1016/j.amjcard.2006.06.058

Urry, E., & Landolt, H. P. (2015). Adenosine, caffeine, and performance: From cognitive neuroscience of sleep to sleep pharmacogenetics. Current Topics in Behavioral Neurosciences, 25, 331-366. https://doi.org/10.1007/7854_2014_274

Valdez, R. C., Ahlawat, R., Wills-Karp, M., Nathan, A., Ezell, T., & Gauda, E. B. (2011). Correlation between serum caffeine levels and changes in cytokine profile in a cohort of preterm infants. Journal of Pediatrics, 158(1), 57-64, 64.e1. https://doi.org/10.1016/j.jpeds.2010.06.051

van Dam, R. M., & Hu, F. B. (2022). Caffeine consumption and cardiovascular health. Nature Reviews. Cardiology, 19(7), 429-430. https://doi.org/10.1038/s41569-022-00719-4

van Furth, A. M., Seijmonsbergen, E. M., Langermans, J. A., van der Meide, P. H., & van Furth, R. (1995). Effect of xanthine derivates and dexamethasone on Streptococcus pneumoniae-stimulated production of tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta), and IL-10 by human leukocytes. Clinical and Diagnostic Laboratory Immunology, 2(6), 689-692. https://doi.org/10.1128/cdli.2.6.689-692.1995

Vanhaesebroeck, B., Leevers, S. J., Ahmadi, K., Timms, J., Katso, R., Driscoll, P. C., Woscholski, R., Parker, P. J., & Waterfield, M. D. (2001). Synthesis and function of 3-phosphorylated inositol lipids. Annual Review of Biochemistry, 70, 535-602. https://doi.org/10.1146/annurev.biochem.70.1.535

Vanhaesebroeck, B., & Waterfield, M. D. (1999). Signaling by distinct classes of phosphoinositide 3-kinases. Experimental Cell Research, 253(1), 239-254. https://doi.org/10.1006/excr.1999.4701

Vargas-Pozada, E. E., Ramos-Tovar, E., Acero-Hernandez, C., Cardoso-Lezama, I., Galindo-Gomez, S., Tsutsumi, V., & Muriel, P. (2023). The antioxidant and anti-inflammatory activities of caffeine effectively attenuate nonalcoholic steatohepatitis and thioacetamide-induced hepatic injury in male rats. Canadian Journal of Physiology and Pharmacology, 101(3), 147-159. https://doi.org/10.1139/cjpp-2022-0303

Vidyasagar, R., Greyling, A., Draijer, R., Corfield, D. R., & Parkes, L. M. (2013). The effect of black tea and caffeine on regional cerebral blood flow measured with arterial spin labeling. Journal of Cerebral Blood Flow and Metabolism, 33(6), 963-968. https://doi.org/10.1038/jcbfm.2013.40

Walaschewski, R., Begrow, F., & Verspohl, E. J. (2013). Impact and benefit of A2B-adenosine receptor agonists for the respiratory tract: Mucociliary clearance, ciliary beat frequency, trachea muscle tonus and cytokine release. Journal of Pharmacy and Pharmacology, 65(1), 123-132. https://doi.org/10.1111/j.2042-7158.2012.01580.x

Wang, H. Q., Song, K. Y., Feng, J. Z., Huang, S. Y., Guo, X. M., Zhang, L., Zhang, G., Huo, Y. C., Zhang, R. R., Ma, Y., Hu, Q. Z., & Qin, X. Y. (2022). Caffeine inhibits activation of the NLRP3 Inflammasome via autophagy to attenuate microglia-mediated Neuroinflammation in experimental autoimmune encephalomyelitis. Journal of Molecular Neuroscience, 72(1), 97-112. https://doi.org/10.1007/s12031-021-01894-8

Wang, P., Jia, J., & Zhang, D. (2020). Purinergic signalling in liver diseases: Pathological functions and therapeutic opportunities. JHEP Rep, 2(6), 100165. https://doi.org/10.1016/j.jhepr.2020.100165

Wang, Q., Dai, X., Yang, W., Wang, H., Zhao, H., Yang, F., Yang, Y., Li, J., & Lv, X. (2015). Caffeine protects against alcohol-induced liver fibrosis by dampening the cAMP/PKA/CREB pathway in rat hepatic stellate cells. International Immunopharmacology, 25(2), 340-352. https://doi.org/10.1016/j.intimp.2015.02.012

Wang, X., Lv, S., Sun, J., Zhang, M., Zhang, L., Sun, Y., Zhao, Z., Wang, D., Zhao, X., & Zhang, J. (2022). Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway. Redox Report, 27(1), 270-278. https://doi.org/10.1080/13510002.2022.2143114

World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR). (2007). Food, nutrition, physical activity, and the prevention of cancer: A global perspective. AICR.

Weichelt, U., Cay, R., Schmitz, T., Strauss, E., Sifringer, M., Buhrer, C., & Endesfelder, S. (2013). Prevention of hyperoxia-mediated pulmonary inflammation in neonatal rats by caffeine. The European Respiratory Journal, 41(4), 966-973. https://doi.org/10.1183/09031936.00012412

Weir, R. L., & Hruska, R. E. (1983). Interaction between methylxanthines and the benzodiazepine receptor. Archives Internationales de Pharmacodynamie et de Thérapie, 265(1), 42-48.

Wendler, C. C., Amatya, S., McClaskey, C., Ghatpande, S., Fredholm, B. B., & Rivkees, S. A. (2007). A1 adenosine receptors play an essential role in protecting the embryo against hypoxia. Proceedings of the National Academy of Sciences of the United States of America, 104(23), 9697-9702. https://doi.org/10.1073/pnas.0703557104

Wentz, C. T., & Magavi, S. S. (2009). Caffeine alters proliferation of neuronal precursors in the adult hippocampus. Neuropharmacology, 56(6-7), 994-1000. https://doi.org/10.1016/j.neuropharm.2009.02.002

White, J. R., Jr., Padowski, J. M., Zhong, Y., Chen, G., Luo, S., Lazarus, P., Layton, M. E., & McPherson, S. (2016). Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults. Clinical Toxicology, 54(4), 308-312.

Willson, C. (2018). The clinical toxicology of caffeine: A review and case study. Toxicology Reports, 5, 1140-1152. https://doi.org/10.1016/j.toxrep.2018.11.002

Wong, C. W., Olafsson, V., Tal, O., & Liu, T. T. (2012). Anti-correlated networks, global signal regression, and the effects of caffeine in resting-state functional MRI. NeuroImage, 63(1), 356-364. https://doi.org/10.1016/j.neuroimage.2012.06.035

Wu, S. E., & Chen, W. L. (2020). Exploring the association between urine caffeine metabolites and urine flow rate: A cross-sectional study. Nutrients, 12(9), 2803. https://doi.org/10.3390/nu12092803

Wu, W., Tong, Y., Zhao, Q., Yu, G., Wei, X., & Lu, Q. (2015). Coffee consumption and bladder cancer: A meta-analysis of observational studies. Scientific Reports, 5, 9051. https://doi.org/10.1038/srep09051

Xie, J., Ponuwei, G. A., Moore, C. E., Willars, G. B., Tee, A. R., & Herbert, T. P. (2011). cAMP inhibits mammalian target of rapamycin complex-1 and -2 (mTORC1 and 2) by promoting complex dissociation and inhibiting mTOR kinase activity. Cellular Signalling, 23(12), 1927-1935. https://doi.org/10.1016/j.cellsig.2011.06.025

Xu, F., Liua, P. Y., Pekar, J. J., & Lu, H. Z. (2015). Does acute caffeine ingestion alter brain metabolism in young adults? NeuroImage, 110, 39-47. https://doi.org/10.1016/j.neuroimage.2015.01.046

Xu, H., Hu, L., Liu, T., Chen, F., Li, J., Xu, J., Jiang, L., Xiang, Z., Wang, X., & Sheng, J. (2020). Caffeine targets G6PDH to disrupt redox homeostasis and inhibit renal cell carcinoma proliferation. Frontiers in Cell and Developmental Biology, 8, 556162.

Xu, Y., Ma, L., Liu, F., Yao, L., Wang, W. C., Yang, S. Z., & Han, T. T. (2023). Lavender essential oil fractions alleviate sleep disorders induced by the combination of anxiety and caffeine in mice. Journal of Ethnopharmacology, 302, 115868. https://doi.org/10.1016/j.jep.2022.115868

Yamashita, A., Ohnishi, T., Kashima, I., Taya, Y., & Ohno, S. (2001). Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay. Genes & Development, 15(17), 2215-2228. https://doi.org/10.1101/gad.913001

Yamauchi, R., Kobayashi, M., Matsuda, Y., Ojika, M., Shigeoka, S., Yamamoto, Y., Tou, Y., Inoue, T., Katagiri, T., Murai, A., & Horio, F. (2010). Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-ay mice. Journal of Agricultural and Food Chemistry, 58(9), 5597-5603. https://doi.org/10.1021/jf904062c

Yang, H., Rouse, J., Lukes, L., Lancaster, M., Veenstra, T., Zhou, M., Shi, Y., Park, Y. G., & Hunter, K. (2004). Caffeine suppresses metastasis in a transgenic mouse model: A prototype molecule for prophylaxis of metastasis. Clinical & Experimental Metastasis, 21(8), 719-735. https://doi.org/10.1007/s10585-004-8251-4

Yang, J., Nie, J., Ma, X. L., Wei, Y. Q., Peng, Y., & Wei, X. W. (2019). Targeting PI3K in cancer: Mechanisms and advances in clinical trials. Molecular Cancer, 18, 26. https://doi.org/10.1186/s12943-019-0954-x

Yang, L., Yu, X. F., Zhang, Y. J., Liu, N., Xue, X. D., & Fu, J. H. (2022). Caffeine treatment started before injury reduces hypoxic-ischemic white-matter damage in neonatal rats by regulating phenotypic microglia polarization. Pediatric Research, 92(6), 1543-1554. https://doi.org/10.1038/s41390-021-01924-6

Yokokawa, T., Hashimoto, T., & Iwanaka, N. (2021). Caffeine increases myoglobin expression via the cyclic AMP pathway in L6 myotubes. Physiological Reports, 9(9), e14869. https://doi.org/10.14814/phy2.14869

Yoo, S., & Dynan, W. S. (1999). Geometry of a complex formed by double strand break repair proteins at a single DNA end: Recruitment of DNA-PKcs induces inward translocation of Ku protein. Nucleic Acids Research, 27(24), 4679-4686.

Youngberg, M. R., Karpov, I. O., Begley, A., Pollock, B. G., & Buysse, D. J. (2011). Clinical and physiological correlates of caffeine and caffeine metabolites in primary insomnia. Journal of Clinical Sleep Medicine, 7(2), 196-203.

Yu, L. Q., Coelho, J. E., Zhang, X. L., Fu, Y. T., Tillman, A., Karaoz, U., Fredholm, B. B., Weng, Z., & Chen, J. F. (2009). Uncovering multiple molecular targets for caffeine using a drug target validation strategy combining a(2A) receptor knockout mice with microarray profiling. Physiological Genomics, 37(3), 199-210. https://doi.org/10.1152/physiolgenomics.90353.2008

Yu, N. Y., Bieder, A., Raman, A., Mileti, E., Katayama, S., Einarsdottir, E., Fredholm, B. B., Falk, A., Tapia-Páez, I., Daub, C. O., & Kere, J. (2017). Acute doses of caffeine shift nervous system cell expression profiles toward promotion of neuronal projection growth. Scientific Reports, 7(1), 11458. https://doi.org/10.1038/s41598-017-11574-6

Yun, J. W., Shin, E. S., Cho, S. Y., Kim, S. H., Kim, C. W., Lee, T. R., & Kim, B. H. (2008). The effects of BADGE and caffeine on the time-course response of adiponectin and lipid oxidative enzymes in high fat diet-fed C57BL/6J mice: Correlation with reduced adiposity and steatosis. Experimental Animals, 57(5), 461-469. https://doi.org/10.1538/expanim.57.461

Zampelas, A., Panagiotakos, D. B., Pitsavos, C., Chrysohoou, C., & Stefanadis, C. (2004). Associations between coffee consumption and inflammatory markers in healthy persons: The ATTICA study. American Journal of Clinical Nutrition, 80(4), 862-867. https://doi.org/10.1093/ajcn/80.4.862

Zapata, F. J., Rebollo-Hernanz, M., Novakofski, J. E., Nakamura, M. T., & Gonzalez de Mejia, E. (2020). Caffeine, but not other phytochemicals, in mate tea (Ilex paraguariensis St. Hilaire) attenuates high-fat-high-sucrose-diet-driven lipogenesis and body fat accumulation. Journal of Functional Foods, 64, 103646. https://doi.org/10.1016/j.jff.2019.103646

Zhang, J., Liu, T., Gupta, A., Spincemaille, P., Nguyen, T. D., & Wang, Y. (2015). Quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) using quantitative susceptibility mapping (QSM). Magnetic Resonance in Medicine, 74(4), 945-952. https://doi.org/10.1002/mrm.25463

Zhang, Z., Hu, G., Caballero, B., Appel, L., & Chen, L. (2011). Habitual coffee consumption and risk of hypertension: A systematic review and meta-analysis of prospective observational studies. The American Journal of Clinical Nutrition, 93(6), 1212-1219. https://doi.org/10.3945/ajcn.110.004044

Zhao, L. G., Li, Z. Y., Feng, G. S., Ji, X. W., Tan, Y. T., Li, H. L., Gunter, M. J., & Xiang, Y. B. (2020). Coffee drinking and cancer risk: An umbrella review of meta-analyses of observational studies. BMC Cancer, 20(1), 101. https://doi.org/10.1186/s12885-020-6561-9

Zhao, W., Ma, L., Cai, C., & Gong, X. (2019). Caffeine inhibits NLRP3 Inflammasome activation by suppressing MAPK/NF-kappaB and A2aR Signaling in LPS-induced THP-1 macrophages. International Journal of Biological Sciences, 15(8), 1571-1581. https://doi.org/10.7150/ijbs.34211

Zhao, Y., Ren, J., Hillier, J., Lu, W., & Jones, E. Y. (2020). Caffeine inhibits Notum activity by binding at the catalytic pocket. Communications Biology, 3(1), 555. https://doi.org/10.1038/s42003-020-01286-5

Zhao, Y., Wu, Z., Zhang, Y., & Zhu, L. (2013). HY-1 induces G(2)/M cell cycle arrest in human colon cancer cells through the ATR-Chk1-Cdc25C and Weel pathways. Cancer Science, 104(8), 1062-1066. https://doi.org/10.1111/cas.12182

Zhu, S., Noviello, C. M., Teng, J., Walsh, R. M., Jr., Kim, J. J., & Hibbs, R. E. (2018). Structure of a human synaptic GABAA receptor. Nature, 559(7712), 67-72. https://doi.org/10.1038/s41586-018-0255-3

Zou, Z., Tao, T., Li, H., & Zhu, X. (2020). mTOR signaling pathway and mTOR inhibitors in cancer: Progress and challenges. Cell & Bioscience, 10, 31. https://doi.org/10.1186/s13578-020-00396-1

Zulli, A., Smith, R. M., Kubatka, P., Novak, J., Uehara, Y., Loftus, H., Qaradakhi, T., Pohanka, M., Kobyliak, N., Zagatina, A., Klimas, J., Hayes, A., La Rocca, G., Soucek, M., & Kruzliak, P. (2016). Caffeine and cardiovascular diseases: Critical review of current research. European Journal of Nutrition, 55(4), 1331-1343. https://doi.org/10.1007/s00394-016-1179-z

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...