Purinergic P2X receptors (P2X) are ATP-gated ion channels that are broadly expressed in the brain, particularly in the hypothalamus. As ionic channels with high permeability to calcium, P2X play an important and active role in neural functions. The hypothalamus contains a number of small nuclei with many molecularly defined types of peptidergic neurons that affect a wide range of physiological functions, including water balance, blood pressure, metabolism, food intake, circadian rhythm, childbirth and breastfeeding, growth, stress, body temperature, and multiple behaviors. P2X are expressed in hypothalamic neurons, astrocytes, tanycytes, and microvessels. This review focuses on cell-type specific expression of P2X in the most important hypothalamic nuclei, such as the supraoptic nucleus (SON), paraventricular nucleus (PVN), suprachiasmatic nucleus (SCN), anteroventral periventricular nucleus (AVPV), anterior hypothalamic nucleus (AHN), arcuate nucleus (ARC), ventromedial hypothalamic nucleus (VMH), dorsomedial hypothalamic nucleus (DMH), tuberomammillary nucleus (TMN), and lateral hypothalamic area (LHA).> The review also notes the possible role of P2X and extracellular ATP in specific hypothalamic functions. The literature summarized here shows that purinergic signaling is involved in the control of the hypothalamic-pituitary endocrine system, the hypothalamic-neurohypophysial system, the circadian systems and nonendocrine hypothalamic functions.

1st Faculty of Medicine Charles University CZ 121 08 Prague Czech Republic

Institute of Physiology Czech Academy of Sciences CZ 142 20 Prague Czech Republic

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Russell J.A. Fifty Years of Advances in Neuroendocrinology. Brain Neurosci. Adv. 2018;2:2398212818812014. doi: 10.1177/2398212818812014. PubMed DOI PMC

Sanchez Jimenez J.G., De Jesus O. Hypothalamic Dysfunction. StatPearls; Treasure Island, FL, USA: 2024.

Steuernagel L., Lam B.Y.H., Klemm P., Dowsett G.K.C., Bauder C.A., Tadross J.A., Hitschfeld T.S., Del Rio Martin A., Chen W., de Solis A.J., et al. HypoMap-a unified single-cell gene expression atlas of the murine hypothalamus. Nat. Metab. 2022;4:1402–1419. doi: 10.1038/s42255-022-00657-y. PubMed DOI PMC

Collo G., North R.A., Kawashima E., Merlo-Pich E., Neidhart S., Surprenant A., Buell G. Cloning OF P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels. J. Neurosci. 1996;16:2495–2507. doi: 10.1523/JNEUROSCI.16-08-02495.1996. PubMed DOI PMC

Tasker J.G., Oliet S.H., Bains J.S., Brown C.H., Stern J.E. Glial regulation of neuronal function: From synapse to systems physiology. J. Neuroendocrinol. 2012;24:566–576. doi: 10.1111/j.1365-2826.2011.02259.x. PubMed DOI PMC

Svobodova I., Bhattaracharya A., Ivetic M., Bendova Z., Zemkova H. Circadian ATP Release in Organotypic Cultures of the Rat Suprachiasmatic Nucleus Is Dependent on P2X7 and P2Y Receptors. Front. Pharmacol. 2018;9:192. doi: 10.3389/fphar.2018.00192. PubMed DOI PMC

Collo G., Neidhart S., Kawashima E., Kosco-Vilbois M., North R.A., Buell G. Tissue distribution of the P2X7 receptor. Neuropharmacology. 1997;36:1277–1283. doi: 10.1016/S0028-3908(97)00140-8. PubMed DOI

Genzen J.R., Platel J.C., Rubio M.E., Bordey A. Ependymal cells along the lateral ventricle express functional P2X(7) receptors. Purinergic Signal. 2009;5:299–307. doi: 10.1007/s11302-009-9143-5. PubMed DOI PMC

Loesch A. On P2X receptors in the brain: Microvessels. Dedicated to the memory of the late Professor Geoffrey Burnstock (1929–2020) Cell Tissue Res. 2021;384:577–588. doi: 10.1007/s00441-021-03411-0. PubMed DOI

Caruso V., Zuccarini M., Di Iorio P., Muhammad I., Ronci M. Metabolic Changes Induced by Purinergic Signaling: Role in Food Intake. Front. Pharmacol. 2021;12:655989. doi: 10.3389/fphar.2021.655989. PubMed DOI PMC

Gao Z., Guan J., Yin S., Liu F. The role of ATP in sleep-wake regulation: In adenosine-dependent and -independent manner. Sleep. Med. 2024;119:147–154. doi: 10.1016/j.sleep.2024.04.031. PubMed DOI

Lemos J.R., Custer E.E., Ortiz-Miranda S. Purinergic receptor types in the hypothalamic-neurohypophysial system. J. Neuroendocrinol. 2018;30:e12588. doi: 10.1111/jne.12588. PubMed DOI PMC

Zemkova H., Balik A., Jindrichova M., Vavra V. Molecular structure of purinergic P2X receptors and their expression in the hypothalamus and pituitary. Physiol. Res. 2008;57((Suppl. 3)):S23–S38. doi: 10.33549/physiolres.931599. PubMed DOI

Stojilkovic S.S. Purinergic regulation of hypothalamopituitary functions. Trends Endocrinol. Metab. 2009;20:460–468. doi: 10.1016/j.tem.2009.05.005. PubMed DOI PMC

Bjelobaba I., Janjic M.M., Stojilkovic S.S. Purinergic signaling pathways in endocrine system. Auton. Neurosci. 2015;191:102–116. doi: 10.1016/j.autneu.2015.04.010. PubMed DOI PMC

Stojilkovic S.S., Zemkova H. P2X receptor channels in endocrine glands. Wiley Interdiscip. Rev. Membr. Transp. Signal. 2013;2:173–180. doi: 10.1002/wmts.89. PubMed DOI PMC

Burnstock G. Purinergic signalling in endocrine organs. Purinergic Signal. 2014;10:189–231. PubMed PMC

Ali A.A.H., Avakian G.A., Gall C.V. The Role of Purinergic Receptors in the Circadian System. Int. J. Mol. Sci. 2020;21:3423. doi: 10.3390/ijms21103423. PubMed DOI PMC

Wang X., Dong Y.T., Hu X.M., Zhang J.Z., Shi N.R., Zuo Y.Q., Wang X. The circadian regulation of extracellular ATP. Purinergic Signal. 2023;19:283–295. doi: 10.1007/s11302-022-09881-3. PubMed DOI PMC

Chen Y.H., Lin S., Jin S.Y., Gao T.M. Extracellular ATP Is a Homeostatic Messenger That Mediates Cell-Cell Communication in Physiological Processes and Psychiatric Diseases. Biol. Psychiatry. 2024;97:41–53. doi: 10.1016/j.biopsych.2024.04.013. PubMed DOI

Moller M., Busch J.R., Jacobsen C., Lundemose S.B., Lynnerup N., Rath M.F., Banner J. The accessory magnocellular neurosecretory system of the rostral human hypothalamus. Cell Tissue Res. 2018;373:487–498. doi: 10.1007/s00441-018-2818-x. PubMed DOI

Voisin D.L., Herbison A.E., Poulain D.A. Central inhibitory effects of muscimol and bicuculline on the milk ejection reflex in the anaesthetized rat. Pt 1J. Physiol. 1995;483:211–224. doi: 10.1113/jphysiol.1995.sp020579. PubMed DOI PMC

Moos F.C. GABA-induced facilitation of the periodic bursting activity of oxytocin neurones in suckled rats. Pt 1J. Physiol. 1995;488:103–114. doi: 10.1113/jphysiol.1995.sp020949. PubMed DOI PMC

Brussaard A.B., Devay P., Leyting-Vermeulen J.L., Kits K.S. Changes in properties and neurosteroid regulation of GABAergic synapses in the supraoptic nucleus during the mammalian female reproductive cycle. Pt 2J. Physiol. 1999;516:513–524. doi: 10.1111/j.1469-7793.1999.0513v.x. PubMed DOI PMC

Jourdain P., Israel J.M., Dupouy B., Oliet S.H., Allard M., Vitiello S., Theodosis D.T., Poulain D.A. Evidence for a hypothalamic oxytocin-sensitive pattern-generating network governing oxytocin neurons in vitro. J. Neurosci. 1998;18:6641–6649. doi: 10.1523/JNEUROSCI.18-17-06641.1998. PubMed DOI PMC

Oliet S.H., Bourque C.W. Mechanosensitive channels transduce osmosensitivity in supraoptic neurons. Nature. 1993;364:341–343. doi: 10.1038/364341a0. PubMed DOI

Israel J.M., Poulain D.A., Oliet S.H. Glutamatergic inputs contribute to phasic activity in vasopressin neurons. J. Neurosci. 2010;30:1221–1232. doi: 10.1523/JNEUROSCI.2948-09.2010. PubMed DOI PMC

Choe K.Y., Han S.Y., Gaub P., Shell B., Voisin D.L., Knapp B.A., Barker P.A., Brown C.H., Cunningham J.T., Bourque C.W. High salt intake increases blood pressure via BDNF-mediated downregulation of KCC2 and impaired baroreflex inhibition of vasopressin neurons. Neuron. 2015;85:549–560. doi: 10.1016/j.neuron.2014.12.048. PubMed DOI PMC

Pow D.V., Morris J.F. Dendrites of hypothalamic magnocellular neurons release neurohypophysial peptides by exocytosis. Neuroscience. 1989;32:435–439. doi: 10.1016/0306-4522(89)90091-2. PubMed DOI

Sabatier N., Caquineau C., Dayanithi G., Bull P., Douglas A.J., Guan X.M., Jiang M., Van der Ploeg L., Leng G. Alpha-melanocyte-stimulating hormone stimulates oxytocin release from the dendrites of hypothalamic neurons while inhibiting oxytocin release from their terminals in the neurohypophysis. J. Neurosci. 2003;23:10351–10358. doi: 10.1523/JNEUROSCI.23-32-10351.2003. PubMed DOI PMC

Taylor J.H., Intorre A.A., French J.A. Vasopressin and Oxytocin Reduce Food Sharing Behavior in Male, but Not Female Marmosets in Family Groups. Front. Endocrinol. 2017;8:181. doi: 10.3389/fendo.2017.00181. PubMed DOI PMC

Iovino M., Messana T., Tortora A., Giusti C., Lisco G., Giagulli V.A., Guastamacchia E., De Pergola G., Triggiani V. Oxytocin Signaling Pathway: From Cell Biology to Clinical Implications. Endocr. Metab. Immune Disord. Drug Targets. 2021;21:91–110. PubMed

Martucci L.L., Launay J.M., Kawakami N., Sicard C., Desvignes N., Dakouane-Giudicelli M., Spix B., Tetu M., Gilmaire F.O., Paulcan S., et al. Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion. Proc. Natl. Acad. Sci. USA. 2023;120:e2213682120. doi: 10.1073/pnas.2213682120. PubMed DOI PMC

Hu H., Zarate C.A., Jr., Verbalis J. Arginine vasopressin in mood disorders: A potential biomarker of disease pathology and a target for pharmacologic intervention. Psychiatry Clin. Neurosci. 2024;78:495–506. doi: 10.1111/pcn.13703. PubMed DOI PMC

Ludwig M. Dendritic release of vasopressin and oxytocin. J. Neuroendocrinol. 1998;10:881–895. doi: 10.1046/j.1365-2826.1998.00279.x. PubMed DOI

Leng G., Ludwig M. Neurotransmitters and peptides: Whispered secrets and public announcements. J. Physiol. 2008;586:5625–5632. doi: 10.1113/jphysiol.2008.159103. PubMed DOI PMC

Kombian S.B., Hirasawa M., Mouginot D., Pittman Q.J. Modulation of synaptic transmission by oxytocin and vasopressin in the supraoptic nucleus. Prog. Brain Res. 2002;139:235–246. PubMed

Kombian S.B., Hirasawa M., Mouginot D., Chen X., Pittman Q.J. Short-term potentiation of miniature excitatory synaptic currents causes excitation of supraoptic neurons. J. Neurophysiol. 2000;83:2542–2553. doi: 10.1152/jn.2000.83.5.2542. PubMed DOI

Brussaard A.B., Kits K.S. Changes in GABAA receptor-mediated synaptic transmission in oxytocin neurons during female reproduction: Plasticity in a neuroendocrine context. Ann. N. Y. Acad. Sci. 1999;868:677–680. doi: 10.1111/j.1749-6632.1999.tb11344.x. PubMed DOI

Li C., Tripathi P.K., Armstrong W.E. Differences in spike train variability in rat vasopressin and oxytocin neurons and their relationship to synaptic activity. Pt 1J. Physiol. 2007;581:221–240. doi: 10.1113/jphysiol.2006.123810. PubMed DOI PMC

Sladek C.D., Kapoor J.R. Neurotransmitter/neuropeptide interactions in the regulation of neurohypophyseal hormone release. Exp. Neurol. 2001;171:200–209. doi: 10.1006/exnr.2001.7779. PubMed DOI

Armstrong W.E. The neurophysiology of neurosecretory cells. Pt 3J. Physiol. 2007;585:645–647. doi: 10.1113/jphysiol.2007.145755. PubMed DOI PMC

Leng G., Brown C.H., Russell J.A. Physiological pathways regulating the activity of magnocellular neurosecretory cells. Progress. Neurobiol. 1999;57:625–655. doi: 10.1016/S0301-0082(98)00072-0. PubMed DOI

Hu B., Bourque C.W. Functional N-Methyl-D-Aspartate and Non-N-Methyl-D-Aspartate Receptors are Expressed by Rat Supraoptic Neurosecretory Cells in vitro. J. Neuroendocrinol. 1991;3:509–514. doi: 10.1111/j.1365-2826.1991.tb00311.x. PubMed DOI

Shibuya I., Kabashima N., Ibrahim N., Setiadji S.V., Ueta Y., Yamashita H. Pre- and postsynaptic modulation of the electrical activity of rat supraoptic neurones. Exp. Physiol. 2000;85:145S–151S. doi: 10.1111/j.1469-445X.2000.tb00018.x. PubMed DOI

Wuarin J.P., Dudek F.E. Patch-clamp analysis of spontaneous synaptic currents in supraoptic neuroendocrine cells of the rat hypothalamus. J. Neurosci. 1993;13:2323–2331. doi: 10.1523/JNEUROSCI.13-06-02323.1993. PubMed DOI PMC

Decavel C., Curras M.C. Increased expression of the N-methyl-D-aspartate receptor subunit, NR1, in immunohistochemically identified magnocellular hypothalamic neurons during dehydration. Neuroscience. 1997;78:191–202. doi: 10.1016/S0306-4522(96)00544-1. PubMed DOI

Boudaba C., Di S., Tasker J.G. Presynaptic noradrenergic regulation of glutamate inputs to hypothalamic magnocellular neurones. J. Neuroendocrinol. 2003;15:803–810. doi: 10.1046/j.1365-2826.2003.01063.x. PubMed DOI

Iremonger K.J., Benediktsson A.M., Bains J.S. Glutamatergic synaptic transmission in neuroendocrine cells: Basic principles and mechanisms of plasticity. Front. Neuroendocrinol. 2010;31:296–306. doi: 10.1016/j.yfrne.2010.03.002. PubMed DOI

Vilhena-Franco T., Valentim-Lima E., Reis L.C., Elias L.L.K., Antunes-Rodrigues J., Mecawi A.S. Role of AMPA and NMDA receptors on vasopressin and oxytocin secretion induced by hypertonic extracellular volume expansion. J. Neuroendocrinol. 2018;30:e12633. doi: 10.1111/jne.12633. PubMed DOI

Brown C.H. Magnocellular Neurons and Posterior Pituitary Function. Compr. Physiol. 2016;6:1701–1741. doi: 10.1002/j.2040-4603.2016.tb00727.x. PubMed DOI

Ferguson A.V., Latchford K.J., Samson W.K. The paraventricular nucleus of the hypothalamus-a potential target for integrative treatment of autonomic dysfunction. Expert. Opin. Ther. Targets. 2008;12:717–727. doi: 10.1517/14728222.12.6.717. PubMed DOI PMC

Rasiah N.P., Loewen S.P., Bains J.S. Windows into stress: A glimpse at emerging roles for CRH(PVN) neurons. Physiol. Rev. 2023;103:1667–1691. doi: 10.1152/physrev.00056.2021. PubMed DOI

Sawchenko P.E., Brown E.R., Chan R.K., Ericsson A., Li H.Y., Roland B.L., Kovacs K.J. The paraventricular nucleus of the hypothalamus and the functional neuroanatomy of visceromotor responses to stress. Prog. Brain Res. 1996;107:201–222. PubMed

Simmons D.M., Swanson L.W. Comparison of the spatial distribution of seven types of neuroendocrine neurons in the rat paraventricular nucleus: Toward a global 3D model. J. Comp. Neurol. 2009;516:423–441. doi: 10.1002/cne.22126. PubMed DOI

Yang Z., Coote J.H. Influence of the hypothalamic paraventricular nucleus on cardiovascular neurones in the rostral ventrolateral medulla of the rat. J. Physiol. 1998;513:521–530. doi: 10.1111/j.1469-7793.1998.521bb.x. PubMed DOI PMC

Shafton A.D., Ryan A., Badoer E. Neurons in the hypothalamic paraventricular nucleus send collaterals to the spinal cord and to the rostral ventrolateral medulla in the rat. Brain Res. 1998;801:239–243. doi: 10.1016/S0006-8993(98)00587-3. PubMed DOI

Sanders J., Nemeroff C. The CRF System as a Therapeutic Target for Neuropsychiatric Disorders. Trends Pharmacol. Sci. 2016;37:1045–1054. doi: 10.1016/j.tips.2016.09.004. PubMed DOI PMC

Marsh N., Marsh A.A., Lee M.R., Hurlemann R. Oxytocin and the Neurobiology of Prosocial Behavior. Neuroscientist. 2021;27:604–619. doi: 10.1177/1073858420960111. PubMed DOI PMC

Borroto-Escuela D.O., Cuesta-Marti C., Lopez-Salas A., Chruscicka-Smaga B., Crespo-Ramirez M., Tesoro-Cruz E., Palacios-Lagunas D.A., Perez de la Mora M., Schellekens H., Fuxe K. The oxytocin receptor represents a key hub in the GPCR heteroreceptor network: Potential relevance for brain and behavior. Front. Mol. Neurosci. 2022;15:1055344. doi: 10.3389/fnmol.2022.1055344. PubMed DOI PMC

Santoso P., Nakata M., Ueta Y., Yada T. Suprachiasmatic vasopressin to paraventricular oxytocin neurocircuit in the hypothalamus relays light reception to inhibit feeding behavior. Am. J. Physiol. Endocrinol. Metab. 2018;315:E478–E488. doi: 10.1152/ajpendo.00338.2016. PubMed DOI

Vargas Y., Castro Tron A.E., Rodriguez Rodriguez A., Uribe R.M., Joseph-Bravo P., Charli J.L. Thyrotropin-Releasing Hormone and Food Intake in Mammals: An Update. Metabolites. 2024;14:302. doi: 10.3390/metabo14060302. PubMed DOI PMC

Nunn N., Womack M., Dart C., Barrett-Jolley R. Function and pharmacology of spinally-projecting sympathetic pre-autonomic neurones in the paraventricular nucleus of the hypothalamus. Curr. Neuropharmacol. 2011;9:262–277. doi: 10.2174/157021107012043159X. PubMed DOI PMC

Strecker G.J., Wuarin J.P., Dudek F.E. GABAA-mediated local synaptic pathways connect neurons in the rat suprachiasmatic nucleus. J. Neurophysiol. 1997;78:2217–2220. doi: 10.1152/jn.1997.78.4.2217. PubMed DOI

Moore R.Y., Eichler V.B. Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res. 1972;42:201–206. doi: 10.1016/0006-8993(72)90054-6. PubMed DOI

Stephan F.K., Zucker I. Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc. Natl. Acad. Sci. USA. 1972;69:1583–1586. doi: 10.1073/pnas.69.6.1583. PubMed DOI PMC

Sumova A., Travnickova Z., Peters R., Schwartz W.J., Illnerova H. The rat suprachiasmatic nucleus is a clock for all seasons. Proc. Natl. Acad. Sci. USA. 1995;92:7754–7758. doi: 10.1073/pnas.92.17.7754. PubMed DOI PMC

Reppert S.M. A clockwork explosion! Neuron. 1998;21:1–4. doi: 10.1016/S0896-6273(00)80234-2. PubMed DOI

Lee H.S., Billings H.J., Lehman M.N. The suprachiasmatic nucleus: A clock of multiple components. J. Biol. Rhythm. 2003;18:435–449. doi: 10.1177/0748730403259106. PubMed DOI

Moore R.Y., Card J.P. Visual pathways and the entrainment of circadian rhythms. Ann. N. Y. Acad. Sci. 1985;453:123–133. doi: 10.1111/j.1749-6632.1985.tb11805.x. PubMed DOI

Jacomy H., Burlet A., Bosler O. Vasoactive intestinal peptide neurons as synaptic targets for vasopressin neurons in the suprachiasmatic nucleus. Double-label immunocytochemical demonstration in the rat. Neuroscience. 1999;88:859–870. doi: 10.1016/S0306-4522(98)00259-0. PubMed DOI

Brancaccio M., Enoki R., Mazuski C.N., Jones J., Evans J.A., Azzi A. Network-mediated encoding of circadian time: The suprachiasmatic nucleus (SCN) from genes to neurons to circuits, and back. J. Neurosci. 2014;34:15192–15199. doi: 10.1523/JNEUROSCI.3233-14.2014. PubMed DOI PMC

Inouye S.T., Kawamura H. Persistence of circadian rhythmicity in a mammalian hypothalamic island containing the suprachiasmatic nucleus. Proc. Natl. Acad. Sci. USA. 1979;76:5962–5966. doi: 10.1073/pnas.76.11.5962. PubMed DOI PMC

Groos G., Hendriks J. Circadian rhythms in electrical discharge of rat suprachiasmatic neurones recorded in vitro. Neurosci. Lett. 1982;34:283–288. doi: 10.1016/0304-3940(82)90189-6. PubMed DOI

Pennartz C.M., de Jeu M.T., Bos N.P., Schaap J., Geurtsen A.M. Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock. Nature. 2002;416:286–290. doi: 10.1038/nature728. PubMed DOI

Stephens S.B.Z., Kauffman A.S. Estrogen Regulation of the Molecular Phenotype and Active Translatome of AVPV Kisspeptin Neurons. Endocrinology. 2021;162:bqab080. doi: 10.1210/endocr/bqab080. PubMed DOI PMC

Spergel D.J. Modulation of Gonadotropin-Releasing Hormone Neuron Activity and Secretion in Mice by Non-peptide Neurotransmitters, Gasotransmitters, and Gliotransmitters. Front. Endocrinol. 2019;10:329. doi: 10.3389/fendo.2019.00329. PubMed DOI PMC

Fu J., Yu Q., Guo W., He C., Burnstock G., Xiang Z. P2X receptors are expressed on neurons containing luteinizing hormone-releasing hormone in the mouse hypothalamus. Neurosci. Lett. 2009;458:32–36. doi: 10.1016/j.neulet.2009.04.017. PubMed DOI

Sarkar D.K., Chiappa S.A., Fink G., Sherwood N.M. Gonadotropin-releasing hormone surge in pro-oestrous rats. Nature. 1976;264:461–463. doi: 10.1038/264461a0. PubMed DOI

Baca-Alonso J.J.A., Quintanar J.L. The effect of gonadotropin-releasing hormone on the nervous system. Neuro Endocrinol. Lett. 2024;45:188–196. PubMed

Bakker J. Can kisspeptin be a new treatment for sexual dysfunction? Trends Endocrinol. Metab. 2025 doi: 10.1016/j.tem.2025.03.002. Online ahead of print . PubMed DOI

Messager S., Chatzidaki E.E., Ma D., Hendrick A.G., Zahn D., Dixon J., Thresher R.R., Malinge I., Lomet D., Carlton M.B., et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc. Natl. Acad. Sci. USA. 2005;102:1761–1766. doi: 10.1073/pnas.0409330102. PubMed DOI PMC

de Roux N., Genin E., Carel J.C., Matsuda F., Chaussain J.L., Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc. Natl. Acad. Sci. USA. 2003;100:10972–10976. doi: 10.1073/pnas.1834399100. PubMed DOI PMC

Sliwowska J.H., Woods N.E., Alzahrani A.R., Paspali E., Tate R.J., Ferro V.A. Kisspeptin a potential therapeutic target in treatment of both metabolic and reproductive dysfunction. J. Diabetes. 2024;16:e13541. doi: 10.1111/1753-0407.13541. PubMed DOI PMC

Boulant J.A., Hardy J.D. The effect of spinal and skin temperatures on the firing rate and thermosensitivity of preoptic neurones. J. Physiol. 1974;240:639–660. doi: 10.1113/jphysiol.1974.sp010627. PubMed DOI PMC

Bouret S.G., Draper S.J., Simerly R.B. Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice. J. Neurosci. 2004;24:2797–2805. doi: 10.1523/JNEUROSCI.5369-03.2004. PubMed DOI PMC

Martins A.B., Brownlow M.L., Araujo B.B., Garnica-Siqueira M.C., Zaia D.A.M., Leite C.M., Zaia C., Uchoa E.T. Arcuate nucleus of the hypothalamus contributes to the hypophagic effect and plasma metabolic changes induced by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Neurochem. Int. 2022;155:105300. doi: 10.1016/j.neuint.2022.105300. PubMed DOI

Fioramonti X., Lorsignol A., Taupignon A., Penicaud L. A new ATP-sensitive K+ channel-independent mechanism is involved in glucose-excited neurons of mouse arcuate nucleus. Diabetes. 2004;53:2767–2775. doi: 10.2337/diabetes.53.11.2767. PubMed DOI

Mehay D., Silberman Y., Arnold A.C. The Arcuate Nucleus of the Hypothalamus and Metabolic Regulation: An Emerging Role for Renin-Angiotensin Pathways. Int. J. Mol. Sci. 2021;22:7050. doi: 10.3390/ijms22137050. PubMed DOI PMC

Dos Santos K.M., Saunders S.E., Antunes V.R., Boychuk C.R. Insulin activates parasympathetic hepatic-related neurons of the paraventricular nucleus of the hypothalamus through mTOR signaling. J. Neurophysiol. 2025;133:320–332. doi: 10.1152/jn.00284.2024. PubMed DOI PMC

Clarkson J., Han S.Y., Piet R., McLennan T., Kane G.M., Ng J., Porteous R.W., Kim J.S., Colledge W.H., Iremonger K.J., et al. Definition of the hypothalamic GnRH pulse generator in mice. Proc. Natl. Acad. Sci. USA. 2017;114:E10216–E10223. doi: 10.1073/pnas.1713897114. PubMed DOI PMC

Goto T., Hagihara M., Miyamichi K. Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice. eLife. 2023;12:e82533. doi: 10.7554/eLife.82533. PubMed DOI PMC

Koysombat K., Tsoutsouki J., Patel A.H., Comninos A.N., Dhillo W.S., Abbara A. Kisspeptin and Neurokinin B: Roles in reproductive health. Physiol. Rev. 2025;105:707–764. doi: 10.1152/physrev.00015.2024. PubMed DOI

Sawchenko P.E., Swanson L.W. The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat. Brain Res. 1982;257:275–325. doi: 10.1016/0165-0173(82)90010-8. PubMed DOI

Mezey E., Kiss J.Z., Mueller G.P., Eskay R., O’Donohue T.L., Palkovits M. Distribution of the pro-opiomelanocortin derived peptides, adrenocorticotrope hormone, alpha-melanocyte-stimulating hormone and beta-endorphin (ACTH, alpha-MSH, beta-END) in the rat hypothalamus. Brain Res. 1985;328:341–347. doi: 10.1016/0006-8993(85)91046-7. PubMed DOI

Morgane P.J. Electrophysiological studies of feeding and satiety centers in the rat. Am. J. Physiol. 1961;201:838–844. doi: 10.1152/ajplegacy.1961.201.5.838. PubMed DOI

King B.M. The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol. Behav. 2006;87:221–244. doi: 10.1016/j.physbeh.2005.10.007. PubMed DOI

Jo Y.H., Donier E., Martinez A., Garret M., Toulme E., Boue-Grabot E. Crosstalk between P2X4 and GABA-A receptors determines synaptic efficacy at central synapses. J. Biol. Chem. 2011;256:19993–20004. doi: 10.1074/jbc.M111.231324. PubMed DOI PMC

Cheung C.C., Kurrasch D.M., Liang J.K., Ingraham H.A. Genetic labeling of steroidogenic factor-1 (SF-1) neurons in mice reveals ventromedial nucleus of the hypothalamus (VMH) circuitry beginning at neurogenesis and development of a separate non-SF-1 neuronal cluster in the ventrolateral VMH. J. Comp. Neurol. 2013;521:1268–1288. doi: 10.1002/cne.23226. PubMed DOI PMC

Sapkota S., Roy S.C., Briski K.P. Dorsomedial Ventromedial Hypothalamic Nucleus Growth Hormone-Releasing Hormone Neuron Steroidogenic Factor-1 Gene Targets in Female Rat. ASN Neuro. 2024;16:2403345. doi: 10.1080/17590914.2024.2403345. PubMed DOI PMC

Fosch A., Zagmutt S., Casals N., Rodriguez-Rodriguez R. New Insights of SF1 Neurons in Hypothalamic Regulation of Obesity and Diabetes. Int. J. Mol. Sci. 2021;22:6186. doi: 10.3390/ijms22126186. PubMed DOI PMC

Bellinger L.L., Bernardis L.L. The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation: Lessons learned from lesioning studies. Physiol. Behav. 2002;76:431–442. doi: 10.1016/S0031-9384(02)00756-4. PubMed DOI

Brasil T.F.S., Lopes-Azevedo S., Belem-Filho I.J.A., Fortaleza E.A.T., Antunes-Rodrigues J., Correa F.M.A. The Dorsomedial Hypothalamus Is Involved in the Mediation of Autonomic and Neuroendocrine Responses to Restraint Stress. Front. Pharmacol. 2019;10:1547. doi: 10.3389/fphar.2019.01547. PubMed DOI PMC

DiMicco J.A., Samuels B.C., Zaretskaia M.V., Zaretsky D.V. The dorsomedial hypothalamus and the response to stress: Part renaissance, part revolution. Pharmacol. Biochem. Behav. 2002;71:469–480. doi: 10.1016/S0091-3057(01)00689-X. PubMed DOI

Sakai K., Takahashi K., Anaclet C., Lin J.S. Sleep-waking discharge of ventral tuberomammillary neurons in wild-type and histidine decarboxylase knock-out mice. Front. Behav. Neurosci. 2010;4:53. doi: 10.3389/fnbeh.2010.00053. PubMed DOI PMC

Wada H., Inagaki N., Itowi N., Yamatodani A. Histaminergic neuron system in the brain: Distribution and possible functions. Brain Res. Bull. 1991;27:367–370. doi: 10.1016/0361-9230(91)90126-5. PubMed DOI

Mickelsen L.E., Bolisetty M., Chimileski B.R., Fujita A., Beltrami E.J., Costanzo J.T., Naparstek J.R., Robson P., Jackson A.C. Single-cell transcriptomic analysis of the lateral hypothalamic area reveals molecularly distinct populations of inhibitory and excitatory neurons. Nat. Neurosci. 2019;22:642–656. doi: 10.1038/s41593-019-0349-8. PubMed DOI PMC

Collden G., Mangano C., Meister B. P2X2 purinoreceptor protein in hypothalamic neurons associated with the regulation of food intake. Neuroscience. 2010;171:62–78. doi: 10.1016/j.neuroscience.2010.08.036. PubMed DOI

Sandoval-Caballero C., Jara J., Luarte L., Jimenez Y., Teske J.A., Perez-Leighton C. Control of motivation for sucrose in the paraventricular hypothalamic nucleus by dynorphin peptides and the kappa opioid receptor. Appetite. 2024;200:107504. doi: 10.1016/j.appet.2024.107504. PubMed DOI

Bernardis L.L., Bellinger L.L. The lateral hypothalamic area revisited: Neuroanatomy, body weight regulation, neuroendocrinology and metabolism. Neurosci. Biobehav. Rev. 1993;17:141–193. doi: 10.1016/S0149-7634(05)80149-6. PubMed DOI

Bonnavion P., Mickelsen L.E., Fujita A., de Lecea L., Jackson A.C. Hubs and spokes of the lateral hypothalamus: Cell types, circuits and behaviour. J. Physiol. 2016;594:6443–6462. doi: 10.1113/JP271946. PubMed DOI PMC

Samson W.K., Taylor M.M., Follwell M., Ferguson A.V. Orexin actions in hypothalamic paraventricular nucleus: Physiological consequences and cellular correlates. Regul. Pept. 2002;104:97–103. doi: 10.1016/S0167-0115(01)00353-6. PubMed DOI

Lopez R., Young S.L., Cox V.C. Analgesia for formalin-induced pain by lateral hypothalamic stimulation. Brain Res. 1991;563:1–6. doi: 10.1016/0006-8993(91)91506-V. PubMed DOI

Khan R., Lee B., Inyang K., Bemis H., Bugescu R., Laumet G., Leinninger G. Neurotensin-expressing lateral hypothalamic neurons alleviate neuropathic and inflammatory pain via neurotensin receptor signaling. Neurobiol. Pain. 2024;16:100172. doi: 10.1016/j.ynpai.2024.100172. PubMed DOI PMC

Beamer E., Conte G., Engel T. ATP release during seizures-A critical evaluation of the evidence. Brain Res. Bull. 2019;151:65–73. doi: 10.1016/j.brainresbull.2018.12.021. PubMed DOI

Juranyi Z., Sperlagh B., Vizi E.S. Involvement of P2 purinoceptors and the nitric oxide pathway in [3H]purine outflow evoked by short-term hypoxia and hypoglycemia in rat hippocampal slices. Brain Res. 1999;823:183–190. doi: 10.1016/S0006-8993(99)01169-5. PubMed DOI

Godoy P.A., Ramirez-Molina O., Fuentealba J. Exploring the Role of P2X Receptors in Alzheimer’s Disease. Front. Pharmacol. 2019;10:1330. doi: 10.3389/fphar.2019.01330. PubMed DOI PMC

Guthrie P.B., Knappenberger J., Segal M., Bennett M.V., Charles A.C., Kater S.B. ATP released from astrocytes mediates glial calcium waves. J. Neurosci. 1999;19:520–528. doi: 10.1523/JNEUROSCI.19-02-00520.1999. PubMed DOI PMC

Fields R.D., Stevens B. ATP: An extracellular signaling molecule between neurons and glia. Trends Neurosci. 2000;23:625–633. doi: 10.1016/S0166-2236(00)01674-X. PubMed DOI

Inoue K., Koizumi S., Tsuda M. The role of nucleotides in the neuron—Glia communication responsible for the brain functions. J. Neurochem. 2007;102:1447–1458. doi: 10.1111/j.1471-4159.2007.04824.x. PubMed DOI

Abbracchio M.P., Burnstock G., Verkhratsky A., Zimmermann H. Purinergic signalling in the nervous system: An overview. Trends Neurosci. 2009;32:19–29. doi: 10.1016/j.tins.2008.10.001. PubMed DOI

Lalo U., Palygin O., Verkhratsky A., Grant S.G., Pankratov Y. ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex. Sci. Rep. 2016;6:33609. doi: 10.1038/srep33609. PubMed DOI PMC

Araque A., Parpura V., Sanzgiri R.P., Haydon P.G. Tripartite synapses: Glia, the unacknowledged partner. Trends Neurosci. 1999;22:208–215. doi: 10.1016/S0166-2236(98)01349-6. PubMed DOI

Crosby K.M., Murphy-Royal C., Wilson S.A., Gordon G.R., Bains J.S., Pittman Q.J. Cholecystokinin Switches the Plasticity of GABA Synapses in the Dorsomedial Hypothalamus via Astrocytic ATP Release. J. Neurosci. 2018;38:8515–8525. doi: 10.1523/JNEUROSCI.0569-18.2018. PubMed DOI PMC

Hong Y., Zhao T., Li X.J., Li S. Mutant Huntingtin Impairs BDNF Release from Astrocytes by Disrupting Conversion of Rab3a-GTP into Rab3a-GDP. J. Neurosci. 2016;36:8790–8801. doi: 10.1523/JNEUROSCI.0168-16.2016. PubMed DOI PMC

Lazarowski E.R., Sesma J.I., Seminario-Vidal L., Kreda S.M. Molecular mechanisms of purine and pyrimidine nucleotide release. Adv. Pharmacol. 2011;61:221–261. PubMed

Lazarowski E.R. Vesicular and conductive mechanisms of nucleotide release. Purinergic Signal. 2012;8:359–373. doi: 10.1007/s11302-012-9304-9. PubMed DOI PMC

Burnstock G., Fredholm B.B., Verkhratsky A. Adenosine and ATP receptors in the brain. Curr. Top. Med. Chem. 2011;11:973–1011. doi: 10.2174/156802611795347627. PubMed DOI

Jo Y.H., Schlichter R. Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat. Neurosci. 1999;2:241–245. doi: 10.1038/6344. PubMed DOI

Norenberg W., Illes P. Neuronal P2X receptors: Localisation and functional properties. Naunyn. Schmiedebergs Arch. Pharmacol. 2000;362:324–339. doi: 10.1007/s002100000311. PubMed DOI

Jang I.S., Rhee J.S., Kubota H., Akaike N. Developmental changes in P2X purinoceptors on glycinergic presynaptic nerve terminals projecting to rat substantia gelatinosa neurones. Pt 2J. Physiol. 2001;536:505–519. doi: 10.1111/j.1469-7793.2001.0505c.xd. PubMed DOI PMC

Rodrigues R.J., Almeida T., Richardson P.J., Oliveira C.R., Cunha R.A. Dual presynaptic control by ATP of glutamate release via facilitatory P2X1, P2X2/3, and P2X3 and inhibitory P2Y1, P2Y2, and/or P2Y4 receptors in the rat hippocampus. J. Neurosci. 2005;25:6286–6295. doi: 10.1523/JNEUROSCI.0628-05.2005. PubMed DOI PMC

Burnstock G. Purinergic cotransmission. Exp. Physiol. 2009;94:20–24. doi: 10.1113/expphysiol.2008.043620. PubMed DOI

Vavra V., Bhattacharya A., Zemkova H. Facilitation of glutamate and GABA release by P2X receptor activation in supraoptic neurons from freshly isolated rat brain slices. Neuroscience. 2011;188:1–12. doi: 10.1016/j.neuroscience.2011.04.067. PubMed DOI

Gordon G.R., Baimoukhametova D.V., Hewitt S.A., Rajapaksha W.R., Fisher T.E., Bains J.S. Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy. Nat. Neurosci. 2005;8:1078–1086. doi: 10.1038/nn1498. PubMed DOI

Fumagalli M., Brambilla R., D’Ambrosi N., Volonte C., Matteoli M., Verderio C., Abbracchio M.P. Nucleotide-mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors. Glia. 2003;43:218–230. doi: 10.1002/glia.10248. PubMed DOI

Pascual O., Casper K.B., Kubera C., Zhang J., Revilla-Sanchez R., Sul J.Y., Takano H., Moss S.J., McCarthy K., Haydon P.G. Astrocytic purinergic signaling coordinates synaptic networks. Science. 2005;310:113–116. doi: 10.1126/science.1116916. PubMed DOI

Pangrsic T., Potokar M., Stenovec M., Kreft M., Fabbretti E., Nistri A., Pryazhnikov E., Khiroug L., Giniatullin R., Zorec R. Exocytotic release of ATP from cultured astrocytes. J. Biol. Chem. 2007;282:28749–28758. doi: 10.1074/jbc.M700290200. PubMed DOI

Stout C.E., Costantin J.L., Naus C.C., Charles A.C. Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J. Biol. Chem. 2002;277:10482–10488. doi: 10.1074/jbc.M109902200. PubMed DOI

Schenk U., Westendorf A.M., Radaelli E., Casati A., Ferro M., Fumagalli M., Verderio C., Buer J., Scanziani E., Grassi F. Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels. Sci. Signal. 2008;1:ra6. doi: 10.1126/scisignal.1160583. PubMed DOI

Iglesias R., Dahl G., Qiu F., Spray D.C., Scemes E. Pannexin 1: The molecular substrate of astrocyte “hemichannels”. J. Neurosci. 2009;29:7092–7097. doi: 10.1523/JNEUROSCI.6062-08.2009. PubMed DOI PMC

Li S., Bjelobaba I., Yan Z., Kucka M., Tomic M., Stojilkovic S.S. Expression and roles of pannexins in ATP release in the pituitary gland. Endocrinology. 2011;152:2342–2352. doi: 10.1210/en.2010-1216. PubMed DOI PMC

Khakh B.S., Sofroniew M.V. Diversity of astrocyte functions and phenotypes in neural circuits. Nat. Neurosci. 2015;18:942–952. doi: 10.1038/nn.4043. PubMed DOI PMC

Kinoshita M., Hirayama Y., Fujishita K., Shibata K., Shinozaki Y., Shigetomi E., Takeda A., Le H.P.N., Hayashi H., Hiasa M., et al. Anti-Depressant Fluoxetine Reveals its Therapeutic Effect Via Astrocytes. EBioMedicine. 2018;32:72–83. doi: 10.1016/j.ebiom.2018.05.036. PubMed DOI PMC

Kawate T., Michel J.C., Birdsong W.T., Gouaux E. Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature. 2009;460:592–598. doi: 10.1038/nature08198. PubMed DOI PMC

Hattori M., Gouaux E. Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature. 2012;485:207–212. doi: 10.1038/nature11010. PubMed DOI PMC

North R.A. Molecular physiology of P2X receptors. Physiol. Rev. 2002;82:1013–1067. doi: 10.1152/physrev.00015.2002. PubMed DOI

Nicke A., Baumert H.G., Rettinger J., Eichele A., Lambrecht G., Mutschler E., Schmalzing G. P2X1 and P2X3 receptors form stable trimers: A novel structural motif of ligand-gated ion channels. EMBO J. 1998;17:3016–3028. doi: 10.1093/emboj/17.11.3016. PubMed DOI PMC

Pelegrin P., Surprenant A. Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J. 2006;25:5071–5082. doi: 10.1038/sj.emboj.7601378. PubMed DOI PMC

Boue-Grabot E., Toulme E., Emerit M.B., Garret M. Subunit-specific coupling between gamma-aminobutyric acid type A and P2X2 receptor channels. J. Biol. Chem. 2004;279:52517–52525. doi: 10.1074/jbc.M410223200. PubMed DOI

Boue-Grabot E., Emerit M.B., Toulme E., Seguela P., Garret M. Cross-talk and co-trafficking between rho1/GABA receptors and ATP-gated channels. J. Biol. Chem. 2004;279:6967–6975. doi: 10.1074/jbc.M307772200. PubMed DOI

Xia R., Mei Z.-Z., Milligan C., Jiang L.H. Inhibitory interaction between P2X4 and GABA(C) rho1 receptors. Biochem. Biophys. Res. Commun. 2008;375:38–43. doi: 10.1016/j.bbrc.2008.07.096. PubMed DOI

Queme L.F., Weyler A.A., Cohen E.R., Hudgins R.C., Jankowski M.P. A dual role for peripheral GDNF signaling in nociception and cardiovascular reflexes in the mouse. Proc. Natl. Acad. Sci. USA. 2020;117:698–707. doi: 10.1073/pnas.1910905116. PubMed DOI PMC

Khakh B.S. Molecular physiology of P2X receptors and ATP signalling at synapses. Nat. Rev. Neurosci. 2001;2:165–174. doi: 10.1038/35058521. PubMed DOI

Stojilkovic S.S., Tomic M., He M.L., Yan Z., Koshimizu T.A., Zemkova H. Molecular dissection of purinergic P2X receptor channels. Ann. N. Y. Acad. Sci. 2005;1048:116–130. doi: 10.1196/annals.1342.011. PubMed DOI

Samways D.S., Li Z., Egan T.M. Principles and properties of ion flow in P2X receptors. Front. Cell Neurosci. 2014;8:6. doi: 10.3389/fncel.2014.00006. PubMed DOI PMC

Khakh B.S., Proctor W.R., Dunwiddie T.V., Labarca C., Lester H.A. Allosteric control of gating and kinetics at P2X(4) receptor channels. J. Neurosci. 1999;19:7289–7299. doi: 10.1523/JNEUROSCI.19-17-07289.1999. PubMed DOI PMC

Coddou C., Yan Z., Obsil T., Huidobro-Toro J.P., Stojilkovic S.S. Activation and regulation of purinergic P2X receptor channels. Pharmacol. Rev. 2011;63:641–683. doi: 10.1124/pr.110.003129. PubMed DOI PMC

Coddou C., Stojilkovic S.S., Huidobro-Toro J.P. Allosteric modulation of ATP-gated P2X receptor channels. Rev. Neurosci. 2011;22:335–354. doi: 10.1515/rns.2011.014. PubMed DOI PMC

Stokes L., Bidula S., Bibic L., Allum E. To Inhibit or Enhance? Is There a Benefit to Positive Allosteric Modulation of P2X Receptors? Front. Pharmacol. 2020;11:627. doi: 10.3389/fphar.2020.00627. PubMed DOI PMC

Illes P., Muller C.E., Jacobson K.A., Grutter T., Nicke A., Fountain S.J., Kennedy C., Schmalzing G., Jarvis M.F., Stojilkovic S.S., et al. Update of P2X receptor properties and their pharmacology: IUPHAR Review 30. Br. J. Pharmacol. 2021;178:489–514. doi: 10.1111/bph.15299. PubMed DOI PMC

Sivcev S., Kudova E., Zemkova H. Neurosteroids as positive and negative allosteric modulators of ligand-gated ion channels: P2X receptor perspective. Neuropharmacology. 2023;234:109542. doi: 10.1016/j.neuropharm.2023.109542. PubMed DOI

Norenberg W., Sobottka H., Hempel C., Plotz T., Fischer W., Schmalzing G., Schaefer M. Positive allosteric modulation by ivermectin of human but not murine P2X7 receptors. Br. J. Pharmacol. 2012;167:48–66. doi: 10.1111/j.1476-5381.2012.01987.x. PubMed DOI PMC

Bianchi B.R., Lynch K.J., Touma E., Niforatos W., Burgard E.C., Alexander K.M., Park H.S., Yu H., Metzger R., Kowaluk E., et al. Pharmacological characterization of recombinant human and rat P2X receptor subtypes. Eur. J. Pharmacol. 1999;376:127–138. doi: 10.1016/S0014-2999(99)00350-7. PubMed DOI

Oury C., Toth-Zsamboki E., Van Geet C., Thys C., Wei L., Nilius B., Vermylen J., Hoylaerts M.F. A natural dominant negative P2X1 receptor due to deletion of a single amino acid residue. J. Biol. Chem. 2000;275:22611–22614. doi: 10.1074/jbc.C000305200. PubMed DOI

Khakh B.S., Bao X.R., Labarca C., Lester H.A. Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds. Nat. Neurosci. 1999;2:322–330. doi: 10.1038/7233. PubMed DOI

Lynch K.J., Touma E., Niforatos W., Kage K.L., Burgard E.C., van Biesen T., Kowaluk E.A., Jarvis M.F. Molecular and functional characterization of human P2X(2) receptors. Mol. Pharmacol. 1999;56:1171–1181. PubMed

Clyne J.D., LaPointe L.D., Hume R.I. The role of histidine residues in modulation of the rat P2X(2) purinoceptor by zinc and pH. Pt 2J. Physiol. 2002;539:347–359. doi: 10.1113/jphysiol.2001.013244. PubMed DOI PMC

Zhong Y., Dunn P.M., Xiang Z., Bo X., Burnstock G. Pharmacological and molecular characterization of P2X receptors in rat pelvic ganglion neurons. Br. J. Pharmacol. 1998;125:771–781. doi: 10.1038/sj.bjp.0702118. PubMed DOI PMC

Haustein M.D., Kracun S., Lu X.H., Shih T., Jackson-Weaver O., Tong X., Xu J., Yang X.W., O’Dell T.J., Marvin J.S., et al. Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway. Neuron. 2014;82:413–429. doi: 10.1016/j.neuron.2014.02.041. PubMed DOI PMC

Kim S.H., Bahia P.K., Patil M., Sutton S., Sowells I., Hadley S.H., Kollarik M., Taylor-Clark T.E. Development of a Mouse Reporter Strain for the Purinergic P2X(2) Receptor. eNeuro. 2020;7:1–15. doi: 10.1523/ENEURO.0203-20.2020. PubMed DOI PMC

Grohmann M., Schumacher M., Gunther J., Singheiser S.M., Nussbaum T., Wildner F., Gerevich Z., Jabs R., Hirnet D., Lohr C., et al. BAC transgenic mice to study the expression of P2X2 and P2Y(1) receptors. Purinergic Signal. 2021;17:449–465. doi: 10.1007/s11302-021-09792-9. PubMed DOI PMC

Kaczmarek-Hajek K., Lorinczi E., Hausmann R., Nicke A. Molecular and functional properties of P2X receptors—Recent progress and persisting challenges. Purinergic Signal. 2012;8:375–417. PubMed PMC

Hugel S., Schlichter R. Presynaptic P2X receptors facilitate inhibitory GABAergic transmission between cultured rat spinal cord dorsal horn neurons. J. Neurosci. 2000;20:2121–2130. doi: 10.1523/JNEUROSCI.20-06-02121.2000. PubMed DOI PMC

Khakh B.S., Gittermann D., Cockayne D.A., Jones A. ATP modulation of excitatory synapses onto interneurons. J. Neurosci. 2003;23:7426–7437. doi: 10.1523/JNEUROSCI.23-19-07426.2003. PubMed DOI PMC

Lewis C., Neidhart S., Holy C., North R.A., Buell G., Surprenant A. Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature. 1995;377:432–435. doi: 10.1038/377432a0. PubMed DOI

Finger T.E., Danilova V., Barrows J., Bartel D.L., Vigers A.J., Stone L., Hellekant G., Kinnamon S.C. ATP signaling is crucial for communication from taste buds to gustatory nerves. Science. 2005;310:1495–1499. doi: 10.1126/science.1118435. PubMed DOI

Cao X., Li L.P., Wang Q., Wu Q., Hu H.H., Zhang M., Fang Y.Y., Zhang J., Li S.J., Xiong W.C., et al. Astrocyte-derived ATP modulates depressive-like behaviors. Nat. Med. 2013;19:773–777. doi: 10.1038/nm.3162. PubMed DOI

Gerevich Z., Zadori Z.S., Koles L., Kopp L., Milius D., Wirkner K., Gyires K., Illes P. Dual effect of acid pH on purinergic P2X3 receptors depends on the histidine 206 residue. J. Biol. Chem. 2007;282:33949–33957. doi: 10.1074/jbc.M705840200. PubMed DOI

Mansoor S.E., Lu W., Oosterheert W., Shekhar M., Tajkhorshid E., Gouaux E. X-ray structures define human P2X(3) receptor gating cycle and antagonist action. Nature. 2016;538:66–71. doi: 10.1038/nature19367. PubMed DOI PMC

Chen C.C., Akopian A.N., Sivilotti L., Colquhoun D., Burnstock G., Wood J.N. A P2X purinoceptor expressed by a subset of sensory neurons. Nature. 1995;377:428–431. doi: 10.1038/377428a0. PubMed DOI

Cook S.P., McCleskey E.W. Desensitization, recovery and Ca(2+)-dependent modulation of ATP-gated P2X receptors in nociceptors. Neuropharmacology. 1997;36:1303–1308. doi: 10.1016/S0028-3908(97)00132-9. PubMed DOI

North R.A. P2X3 receptors and peripheral pain mechanisms. Pt 2J. Physiol. 2004;554:301–308. doi: 10.1113/jphysiol.2003.048587. PubMed DOI PMC

Ding S., Zhu L., Tian Y., Zhu T., Huang X., Zhang X. P2X3 receptor involvement in endometriosis pain via ERK signaling pathway. PLoS ONE. 2017;12:e0184647. doi: 10.1371/journal.pone.0184647. PubMed DOI PMC

Zheng X.B., Zhang Y.L., Li Q., Liu Y.G., Wang X.D., Yang B.L., Zhu G.C., Zhou C.F., Gao Y., Liu Z.X. Effects of 1,8-cineole on neuropathic pain mediated by P2X2 receptor in the spinal cord dorsal horn. Sci. Rep. 2019;9:7909. doi: 10.1038/s41598-019-44282-4. PubMed DOI PMC

North R.A. P2X receptors. Philos. Trans. R Soc. Lond. B Biol. Sci. 2016;371:20150427. doi: 10.1098/rstb.2015.0427. PubMed DOI PMC

Silva-Ramos M., Silva I., Faria M., Ferreirinha F., Correia-de-Sa P. Activation of Prejunctional P2x2/3 Heterotrimers by ATP Enhances the Cholinergic Tone in Obstructed Human Urinary Bladders. J. Pharmacol. Exp. Ther. 2020;372:63–72. doi: 10.1124/jpet.119.261610. PubMed DOI

Khakh B.S., North R.A. P2X receptors as cell-surface ATP sensors in health and disease. Nature. 2006;442:527–532. doi: 10.1038/nature04886. PubMed DOI

Qureshi O.S., Paramasivam A., Yu J.C., Murrell-Lagnado R.D. Regulation of P2X4 receptors by lysosomal targeting, glycan protection and exocytosis. Pt 21J. Cell Sci. 2007;120:3838–3849. doi: 10.1242/jcs.010348. PubMed DOI

Huang P., Zou Y., Zhong X.Z., Cao Q., Zhao K., Zhu M.X., Murrell-Lagnado R., Dong X.P. P2X4 forms functional ATP-activated cation channels on lysosomal membranes regulated by luminal pH. J. Biol. Chem. 2014;289:17658–17667. doi: 10.1074/jbc.M114.552158. PubMed DOI PMC

Stoop R., Surprenant A., North R.A. Different sensitivities to pH of ATP-induced currents at four cloned P2X receptors. J. Neurophysiol. 1997;78:1837–1840. doi: 10.1152/jn.1997.78.4.1837. PubMed DOI

Jelinkova I., Vavra V., Jindrichova M., Obsil T., Zemkova H.W., Zemkova H., Stojilkovic S.S. Identification of P2X(4) receptor transmembrane residues contributing to channel gating and interaction with ivermectin. Pflug. Arch. 2008;456:939–950. doi: 10.1007/s00424-008-0450-4. PubMed DOI

Buell G., Lewis C., Collo G., North R.A., Surprenant A. An antagonist-insensitive P2X receptor expressed in epithelia and brain. EMBO J. 1996;15:55–62. doi: 10.1002/j.1460-2075.1996.tb00333.x. PubMed DOI PMC

Jelinkova I., Yan Z., Liang Z., Moonat S., Teisinger J., Stojilkovic S.S., Zemkova H. Identification of P2X(4) receptor-specific residues contributing to the ivermectin effects on channel deactivation. Biochem. Biophys. Res. Commun. 2006;349:619–625. doi: 10.1016/j.bbrc.2006.08.084. PubMed DOI

Le K.T., Babinski K., Seguela P. Central P2X4 and P2X6 channel subunits coassemble into a novel heteromeric ATP receptor. J. Neurosci. 1998;18:7152–7159. doi: 10.1523/JNEUROSCI.18-18-07152.1998. PubMed DOI PMC

Seguela P., Haghighi A., Soghomonian J.J., Cooper E. A novel neuronal P2x ATP receptor ion channel with widespread distribution in the brain. J. Neurosci. 1996;16:448–455. doi: 10.1523/JNEUROSCI.16-02-00448.1996. PubMed DOI PMC

Srivastava P., Cronin C.G., Scranton V.L., Jacobson K.A., Liang B.T., Verma R. Neuroprotective and neuro-rehabilitative effects of acute purinergic receptor P2X4 (P2X4R) blockade after ischemic stroke. Exp. Neurol. 2020;329:113308. doi: 10.1016/j.expneurol.2020.113308. PubMed DOI PMC

Montilla A., Mata G.P., Matute C., Domercq M. Contribution of P2X4 Receptors to CNS Function and Pathophysiology. Int. J. Mol. Sci. 2020;21:5562. doi: 10.3390/ijms21155562. PubMed DOI PMC

Kotnis S., Bingham B., Vasilyev D.V., Miller S.W., Bai Y., Yeola S., Chanda P.K., Bowlby M.R., Kaftan E.J., Samad T.A., et al. Genetic and functional analysis of human P2X5 reveals a distinct pattern of exon 10 polymorphism with predominant expression of the nonfunctional receptor isoform. Mol. Pharmacol. 2010;77:953–960. doi: 10.1124/mol.110.063636. PubMed DOI

Guo W., Zhang Z., Liu X., Burnstock G., Xiang Z., He C. Developmental expression of P2X5 receptors in the mouse prenatal central and peripheral nervous systems. Purinergic Signal. 2013;9:239–248. doi: 10.1007/s11302-012-9346-z. PubMed DOI PMC

Guo W., Xu X., Gao X., Burnstock G., He C., Xiang Z. Expression of P2X5 receptors in the mouse CNS. Neuroscience. 2008;156:673–692. doi: 10.1016/j.neuroscience.2008.07.062. PubMed DOI

Ryten M., Dunn P.M., Neary J.T., Burnstock G. ATP regulates the differentiation of mammalian skeletal muscle by activation of a P2X5 receptor on satellite cells. J. Cell Biol. 2002;158:345–355. doi: 10.1083/jcb.200202025. PubMed DOI PMC

Kim H., Kajikawa T., Walsh M.C., Takegahara N., Jeong Y.H., Hajishengallis G., Choi Y. The purinergic receptor P2X5 contributes to bone loss in experimental periodontitis. BMB Rep. 2018;51:468–473. doi: 10.5483/BMBRep.2018.51.9.126. PubMed DOI PMC

Soto F., Garcia-Guzman M., Karschin C., Stuhmer W. Cloning and tissue distribution of a novel P2X receptor from rat brain. Biochem. Biophys. Res. Commun. 1996;223:456–460. doi: 10.1006/bbrc.1996.0915. PubMed DOI

North R. P2X receptors: A third major class of ligand-gated ion channels. Ciba Found. Symp. 1996;198:91–105. PubMed

King B.F., Townsend-Nicholson A., Wildman S.S., Thomas T., Spyer K.M., Burnstock G. Coexpression of rat P2X2 and P2X6 subunits in Xenopus oocytes. J. Neurosci. 2000;20:4871–4877. doi: 10.1523/JNEUROSCI.20-13-04871.2000. PubMed DOI PMC

Torres G.E., Egan T.M., Voigt M.M. Identification of a domain involved in ATP-gated ionotropic receptor subunit assembly. J. Biol. Chem. 1999;274:22359–22365. doi: 10.1074/jbc.274.32.22359. PubMed DOI

Surprenant A., Rassendren F., Kawashima E., North R.A., Buell G. The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7) Science. 1996;272:735–738. doi: 10.1126/science.272.5262.735. PubMed DOI

Virginio C., MacKenzie A., Rassendren F.A., North R.A., Surprenant A. Pore dilation of neuronal P2X receptor channels. Nat. Neurosci. 1999;2:315–321. doi: 10.1038/7225. PubMed DOI

Cheewatrakoolpong B., Gilchrest H., Anthes J.C., Greenfeder S. Identification and characterization of splice variants of the human P2X7 ATP channel. Biochem. Biophys. Res. Commun. 2005;332:17–27. doi: 10.1016/j.bbrc.2005.04.087. PubMed DOI

Adinolfi E., Cirillo M., Woltersdorf R., Falzoni S., Chiozzi P., Pellegatti P., Callegari M.G., Sandona D., Markwardt F., Schmalzing G., et al. Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J. 2010;24:3393–3404. doi: 10.1096/fj.09-153601. PubMed DOI

Di Virgilio F., Schmalzing G., Markwardt F. The Elusive P2X7 Macropore. Trends Cell Biol. 2018;28:392–404. doi: 10.1016/j.tcb.2018.01.005. PubMed DOI

Gelin C.F., Bhattacharya A., Letavic M.A. P2X7 receptor antagonists for the treatment of systemic inflammatory disorders. Prog. Med. Chem. 2020;59:63–99. PubMed

Miras-Portugal M.T., Sebastian-Serrano A., de Diego Garcia L., Diaz-Hernandez M. Neuronal P2X7 Receptor: Involvement in Neuronal Physiology and Pathology. J. Neurosci. 2017;37:7063–7072. doi: 10.1523/JNEUROSCI.3104-16.2017. PubMed DOI PMC

Kopp R., Krautloher A., Ramirez-Fernandez A., Nicke A. P2X7 Interactions and Signaling-Making Head or Tail of It. Front. Mol. Neurosci. 2019;12:183. doi: 10.3389/fnmol.2019.00183. PubMed DOI PMC

Bartlett R., Stokes L., Sluyter R. The P2X7 receptor channel: Recent developments and the use of P2X7 antagonists in models of disease. Pharmacol. Rev. 2014;66:638–675. doi: 10.1124/pr.113.008003. PubMed DOI

Bhattacharya A., Lord B., Grigoleit J.S., He Y., Fraser I., Campbell S.N., Taylor N., Aluisio L., O’Connor J.C., Papp M., et al. Neuropsychopharmacology of JNJ-55308942, evaluation of a clinical candidate targeting P2X7 ion channels in animal models of neuroinflammation and anhedonia. Neuropsychopharmacology. 2018;43:2586–2596. doi: 10.1038/s41386-018-0141-6. PubMed DOI PMC

Czamara D., Muller-Myhsok B., Lucae S. The P2RX7 polymorphism rs2230912 is associated with depression: A meta-analysis. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2018;82:272–277. doi: 10.1016/j.pnpbp.2017.11.003. PubMed DOI

Deussing J.M., Arzt E. P2X7 Receptor: A Potential Therapeutic Target for Depression? Trends Mol. Med. 2018;24:736–747. doi: 10.1016/j.molmed.2018.07.005. PubMed DOI

Bhattacharya A., Biber K. The microglial ATP-gated ion channel P2X7 as a CNS drug target. Glia. 2016;64:1772–1787. doi: 10.1002/glia.23001. PubMed DOI

Bhattacharya A., Ceusters M. Targeting neuroinflammation with brain penetrant P2X7 antagonists as novel therapeutics for neuropsychiatric disorders. Neuropsychopharmacology. 2020;45:234–235. doi: 10.1038/s41386-019-0502-9. PubMed DOI PMC

Illes P., Verkhratsky A., Tang Y. Pathological ATPergic Signaling in Major Depression and Bipolar Disorder. Front. Mol. Neurosci. 2019;12:331. doi: 10.3389/fnmol.2019.00331. PubMed DOI PMC

Liu J., Liu T.T., Mou L., Zhang Y., Chen X., Wang Q., Deng B.L., Liu J. P2X7 receptor: A potential target for treating comorbid anxiety and depression. Purinergic Signal. 2024:1–11. doi: 10.1007/s11302-024-10007-0. PubMed DOI

Vereczkei A., Abdul-Rahman O., Halmai Z., Nagy G., Szekely A., Somogyi A., Faludi G., Nemoda Z. Association of purinergic receptor P2RX7 gene polymorphisms with depression symptoms. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2019;92:207–216. doi: 10.1016/j.pnpbp.2019.01.006. PubMed DOI

Zorina-Lichtenwalter K., Ase A.R., Verma V., Parra A.I.M., Komarova S., Khadra A., Seguela P., Diatchenko L. Characterization of Common Genetic Variants in P2RX7 and Their Contribution to Chronic Pain Conditions. J. Pain. 2024;25:545–556. doi: 10.1016/j.jpain.2023.09.011. PubMed DOI

Jimenez-Pacheco A., Diaz-Hernandez M., Arribas-Blazquez M., Sanz-Rodriguez A., Olivos-Ore L.A., Artalejo A.R., Alves M., Letavic M., Miras-Portugal M.T., Conroy R.M., et al. Transient P2X7 Receptor Antagonism Produces Lasting Reductions in Spontaneous Seizures and Gliosis in Experimental Temporal Lobe Epilepsy. J. Neurosci. 2016;36:5920–5932. doi: 10.1523/JNEUROSCI.4009-15.2016. PubMed DOI PMC

Kaczmarek-Hajek K., Zhang J., Kopp R., Grosche A., Rissiek B., Saul A., Bruzzone S., Engel T., Jooss T., Krautloher A., et al. Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody. eLife. 2018;7:e36217. doi: 10.7554/eLife.36217. PubMed DOI PMC

Ortega F., Gomez-Villafuertes R., Benito-Leon M., Martinez de la Torre M., Olivos-Ore L.A., Arribas-Blazquez M., Gomez-Gaviro M.V., Azcorra A., Desco M., Artalejo A.R., et al. Salient brain entities labelled in P2rx7-EGFP reporter mouse embryos include the septum, roof plate glial specializations and circumventricular ependymal organs. Brain Struct. Funct. 2021;226:715–741. doi: 10.1007/s00429-020-02204-5. PubMed DOI PMC

Shibuya I., Tanaka K., Hattori Y., Uezono Y., Harayama N., Noguchi J., Ueta Y., Izumi F., Yamashita H. Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurones. Pt 2J. Physiol. 1999;514:351–367. doi: 10.1111/j.1469-7793.1999.351ae.x. PubMed DOI PMC

Housley G.D., Kanjhan R., Raybould N.P., Greenwood D., Salih S.G., Jarlebark L., Burton L.D., Setz V.C., Cannell M.B., Soeller C., et al. Expression of the P2X(2) receptor subunit of the ATP-gated ion channel in the cochlea: Implications for sound transduction and auditory neurotransmission. J. Neurosci. 1999;19:8377–8388. doi: 10.1523/JNEUROSCI.19-19-08377.1999. PubMed DOI PMC

Vulchanova L., Arvidsson U., Riedl M., Wang J., Buell G., Surprenant A., North R.A., Elde R. Differential distribution of two ATP-gated channels (P2X receptors) determined by immunocytochemistry. Proc. Natl. Acad. Sci. USA. 1996;93:8063–8067. doi: 10.1073/pnas.93.15.8063. PubMed DOI PMC

Xiang Z., Bo X., Oglesby I., Ford A., Burnstock G. Localization of ATP-gated P2X2 receptor immunoreactivity in the rat hypothalamus. Brain Res. 1998;813:390–397. doi: 10.1016/S0006-8993(98)01073-7. PubMed DOI

Bhattacharya A., Vavra V., Svobodova I., Bendova Z., Vereb G., Zemkova H. Potentiation of inhibitory synaptic transmission by extracellular ATP in rat suprachiasmatic nuclei. J. Neurosci. 2013;33:8035–8044. doi: 10.1523/JNEUROSCI.4682-12.2013. PubMed DOI PMC

Lommen J., Stahr A., Ingenwerth M., Ali A.A.H., von Gall C. Time-of-day-dependent expression of purinergic receptors in mouse suprachiasmatic nucleus. Cell Tissue Res. 2017;369:579–590. doi: 10.1007/s00441-017-2634-8. PubMed DOI PMC

Loesch A., Miah S., Burnstock G. Ultrastructural localisation of ATP-gated P2X2 receptor immunoreactivity in the rat hypothalamo-neurohypophysial system. J. Neurocytol. 1999;28:495–504. doi: 10.1023/A:1007009222518. PubMed DOI

Knott T.K., Velazquez-Marrero C., Lemos J.R. ATP elicits inward currents in isolated vasopressinergic neurohypophysial terminals via P2X2 and P2X3 receptors. Pflug. Arch. 2005;450:381–389. doi: 10.1007/s00424-005-1471-x. PubMed DOI

Guo W., Sun J., Xu X., Bunstock G., He C., Xiang Z. P2X receptors are differentially expressed on vasopressin- and oxytocin-containing neurons in the supraoptic and paraventricular nuclei of rat hypothalamus. Histochem. Cell Biol. 2009;131:29–41. doi: 10.1007/s00418-008-0493-9. PubMed DOI

Knott T.K., Hussy N., Cuadra A.E., Lee R.H., Ortiz-Miranda S., Custer E.E., Lemos J.R. Adenosine trisphosphate appears to act via different receptors in terminals versus somata of the hypothalamic neurohypophysial system. J. Neuroendocrinol. 2012;24:681–689. doi: 10.1111/j.1365-2826.2012.02293.x. PubMed DOI PMC

Xiang Z., He C., Burnstock G. P2X5 receptors are expressed on neurons containing arginine vasopressin and nitric oxide synthase in the rat hypothalamus. Brain Res. 2006;1099:56–63. doi: 10.1016/j.brainres.2006.04.126. PubMed DOI

Loesch A., Burnstock G. Immunoreactivity to P2X(6) receptors in the rat hypothalamo- neurohypophysial system: An ultrastructural study with extravidin and colloidal gold-silver labelling. Neuroscience. 2001;106:621–631. doi: 10.1016/S0306-4522(01)00288-3. PubMed DOI

Gomes D.A., Song Z., Stevens W., Sladek C.D. Sustained stimulation of vasopressin and oxytocin release by ATP and phenylephrine requires recruitment of desensitization-resistant P2X purinergic receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009;297:R940–R949. doi: 10.1152/ajpregu.00358.2009. PubMed DOI PMC

Cuadra A.E., Custer E.E., Bosworth E.L., Lemos J.R. P2X7 receptors in neurohypophysial terminals: Evidence for their role in arginine-vasopressin secretion. J. Cell Physiol. 2014;229:333–342. doi: 10.1002/jcp.24453. PubMed DOI PMC

Chen Z.P., Levy A., Lightman S.L. Activation of specific ATP receptors induces a rapid increase in intracellular calcium ions in rat hypothalamic neurons. Brain Res. 1994;641:249–256. doi: 10.1016/0006-8993(94)90151-1. PubMed DOI

Troadec J.D., Thirion S., Nicaise G., Lemos J.R., Dayanithi G. ATP-evoked increases in [Ca2+]i and peptide release from rat isolated neurohypophysial terminals via a P2X2 purinoceptor. Pt 1J. Physiol. 1998;511:89–103. doi: 10.1111/j.1469-7793.1998.089bi.x. PubMed DOI PMC

Song Z., Vijayaraghavan S., Sladek C.D. ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and P2Y purinergic receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007;292:R423–R431. doi: 10.1152/ajpregu.00495.2006. PubMed DOI

Espallergues J., Solovieva O., Techer V., Bauer K., Alonso G., Vincent A., Hussy N. Synergistic activation of astrocytes by ATP and norepinephrine in the rat supraoptic nucleus. Neuroscience. 2007;148:712–723. doi: 10.1016/j.neuroscience.2007.03.043. PubMed DOI

Sladek C.D., Song Z. Diverse roles of G-protein coupled receptors in the regulation of neurohypophyseal hormone secretion. J. Neuroendocrinol. 2012;24:554–565. doi: 10.1111/j.1365-2826.2011.02268.x. PubMed DOI PMC

Day T.A., Sibbald J.R., Khanna S. ATP mediates an excitatory noradrenergic neuron input to supraoptic vasopressin cells. Brain Res. 1993;607:341–344. doi: 10.1016/0006-8993(93)91528-Z. PubMed DOI

Hiruma H., Bourque C.W. P2 purinoceptor-mediated depolarization of rat supraoptic neurosecretory cells in vitro. Pt 3J. Physiol. 1995;489:805–811. doi: 10.1113/jphysiol.1995.sp021093. PubMed DOI PMC

Ivetic M., Bhattacharyya A., Zemkova H. P2X2 Receptor Expression and Function Is Upregulated in the Rat Supraoptic Nucleus Stimulated Through Refeeding After Fasting. Front. Cell Neurosci. 2019;13:284. doi: 10.3389/fncel.2019.00284. PubMed DOI PMC

Mori M., Tsushima H., Matsuda T. Antidiuretic effects of ATP induced by microinjection into the hypothalamic supraoptic nucleus in water-loaded and ethanol-anesthetized rats. Jpn. J. Pharmacol. 1994;66:445–450. doi: 10.1254/jjp.66.445. PubMed DOI

Kapoor J.R., Sladek C.D. Purinergic and adrenergic agonists synergize in stimulating vasopressin and oxytocin release. J. Neurosci. 2000;20:8868–8875. doi: 10.1523/JNEUROSCI.20-23-08868.2000. PubMed DOI PMC

Buller K.M., Khanna S., Sibbald J.R., Day T.A. Central noradrenergic neurons signal via ATP to elicit vasopressin responses to haemorrhage. Neuroscience. 1996;73:637–642. doi: 10.1016/0306-4522(96)00156-X. PubMed DOI

Sperlagh B., Mergl Z., Juranyi Z., Vizi E.S., Makara G.B. Local regulation of vasopressin and oxytocin secretion by extracellular ATP in the isolated posterior lobe of the rat hypophysis. J. Endocrinol. 1999;160:343–350. doi: 10.1677/joe.0.1600343. PubMed DOI

Knott T.K., Marrero H.G., Custer E.E., Lemos J.R. Endogenous ATP potentiates only vasopressin secretion from neurohypophysial terminals. J. Cell Physiol. 2008;217:155–161. doi: 10.1002/jcp.21485. PubMed DOI

Custer E.E., Knott T.K., Cuadra A.E., Ortiz-Miranda S., Lemos J.R. P2X purinergic receptor knockout mice reveal endogenous ATP modulation of both vasopressin and oxytocin release from the intact neurohypophysis. J. Neuroendocrinol. 2012;24:674–680. doi: 10.1111/j.1365-2826.2012.02299.x. PubMed DOI PMC

Yoshimura M., Ohkubo J., Katoh A., Ohno M., Ishikura T., Kakuma T., Yoshimatsu H., Murphy D., Ueta Y. A c-fos-monomeric red fluorescent protein 1 fusion transgene is differentially expressed in rat forebrain and brainstem after chronic dehydration and rehydration. J. Neuroendocrinol. 2013;25:478–487. doi: 10.1111/jne.12022. PubMed DOI

Edgar R.S., Green E.W., Zhao Y., van Ooijen G., Olmedo M., Qin X., Xu Y., Pan M., Valekunja U.K., Feeney K.A., et al. Peroxiredoxins are conserved markers of circadian rhythms. Nature. 2012;485:459–464. doi: 10.1038/nature11088. PubMed DOI PMC

Gottlieb H.B., Ji L.L., Cunningham J.T. Role of superior laryngeal nerve and Fos staining following dehydration and rehydration in the rat. Physiol. Behav. 2011;104:1053–1058. doi: 10.1016/j.physbeh.2011.07.008. PubMed DOI PMC

Carreno F.R., Walch J.D., Dutta M., Nedungadi T.P., Cunningham J.T. Brain-derived neurotrophic factor-tyrosine kinase B pathway mediates NMDA receptor NR2B subunit phosphorylation in the supraoptic nuclei following progressive dehydration. J. Neuroendocrinol. 2011;23:894–905. doi: 10.1111/j.1365-2826.2011.02209.x. PubMed DOI PMC

Lucio-Oliveira F., Traslavina G.A., Borges B.D., Franci C.R. Modulation of the activity of vasopressinergic neurons by estrogen in rats refed with normal or sodium-free food after fasting. Neuroscience. 2015;284:325–336. doi: 10.1016/j.neuroscience.2014.09.076. PubMed DOI

Yao S.T., Gourine A.V., Spyer K.M., Barden J.A., Lawrence A.J. Localisation of P2X2 receptor subunit immunoreactivity on nitric oxide synthase expressing neurones in the brain stem and hypothalamus of the rat: A fluorescence immunohistochemical study. Neuroscience. 2003;121:411–419. doi: 10.1016/S0306-4522(03)00435-4. PubMed DOI

Cham J.L., Owens N.C., Barden J.A., Lawrence A.J., Badoer E. P2X purinoceptor subtypes on paraventricular nucleus neurones projecting to the rostral ventrolateral medulla in the rat. Exp. Physiol. 2006;91:403–411. doi: 10.1113/expphysiol.2005.032409. PubMed DOI

Ferreira-Neto H.C., Ribeiro I.M., Moreira T.S., Yao S.T., Antunes V.R. Purinergic P2 receptors in the paraventricular nucleus of the hypothalamus are involved in hyperosmotic-induced sympathoexcitation. Neuroscience. 2017;349:253–263. doi: 10.1016/j.neuroscience.2017.02.054. PubMed DOI

Du D., Jiang M., Liu M., Wang J., Xia C., Guan R., Shen L., Ji Y., Zhu D. Microglial P2X(7) receptor in the hypothalamic paraventricular nuclei contributes to sympathoexcitatory responses in acute myocardial infarction rat. Neurosci. Lett. 2015;587:22–28. doi: 10.1016/j.neulet.2014.12.026. PubMed DOI

Jacques-Silva M.C., Bernardi A., Rodnight R., Lenz G. ERK, PKC and PI3K/Akt pathways mediate extracellular ATP and adenosine-induced proliferation of U138-MG human glioma cell line. Oncology. 2004;67:450–459. doi: 10.1159/000082930. PubMed DOI

Bains J.S., Oliet S.H. Glia: They make your memories stick! Trends Neurosci. 2007;30:417–424. doi: 10.1016/j.tins.2007.06.007. PubMed DOI

Gordon G.R., Iremonger K.J., Kantevari S., Ellis-Davies G.C., MacVicar B.A., Bains J.S. Astrocyte-mediated distributed plasticity at hypothalamic glutamate synapses. Neuron. 2009;64:391–403. doi: 10.1016/j.neuron.2009.10.021. PubMed DOI PMC

Ferreira-Neto H.C., Antunes V.R., Stern J.E. Purinergic P2 and glutamate NMDA receptor coupling contributes to osmotically driven excitability in hypothalamic magnocellular neurosecretory neurons. J. Physiol. 2021;599:3531–3547. doi: 10.1113/JP281411. PubMed DOI PMC

Whitlock A., Burnstock G., Gibb A.J. The single-channel properties of purinergic P2X ATP receptors in outside-out patches from rat hypothalamic paraventricular parvocells. Pflug. Arch. 2001;443:115–122. doi: 10.1007/s004240100624. PubMed DOI

Ferreira-Neto H.C., Antunes V.R., Stern J.E. ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents. J. Neurophysiol. 2015;114:159–169. doi: 10.1152/jn.01011.2014. PubMed DOI PMC

Xu J., Bernstein A.M., Wong A., Lu X.H., Khoja S., Yang X.W., Davies D.L., Micevych P., Sofroniew M.V., Khakh B.S. P2X4 Receptor Reporter Mice: Sparse Brain Expression and Feeding-Related Presynaptic Facilitation in the Arcuate Nucleus. J. Neurosci. 2016;36:8902–8920. doi: 10.1523/JNEUROSCI.1496-16.2016. PubMed DOI PMC

Mori M., Tsushima H., Matsuda T. Antidiuretic effects of purinoceptor agonists injected into the hypothalamic paraventricular nucleus of water-loaded, ethanol-anesthetized rats. Neuropharmacology. 1992;31:585–592. doi: 10.1016/0028-3908(92)90191-Q. PubMed DOI

Cruz J.C., Bonagamba L.G., Machado B.H. Modulation of arterial pressure by P2 purinoceptors in the paraventricular nucleus of the hypothalamus of awake rats. Auton. Neurosci. Basic Clin. 2010;158:79–85. doi: 10.1016/j.autneu.2010.06.012. PubMed DOI

Minczuk K., Schlicker E., Krzyzewska A., Malinowska B. Angiotensin 1-7 injected into the rat paraventricular nucleus of hypothalamus increases blood pressure and heart rate via various receptors. Neuropharmacology. 2024;266:110279. doi: 10.1016/j.neuropharm.2024.110279. PubMed DOI

Busnardo C., Ferreira-Junior N.C., Cruz J.C., Machado B.H., Correa F.M., Resstel L.B. Cardiovascular responses to ATP microinjected into the paraventricular nucleus are mediated by nitric oxide and NMDA glutamate receptors in awake rats. Exp. Physiol. 2013;98:1411–1421. doi: 10.1113/expphysiol.2013.073619. PubMed DOI

Ferreira-Neto H.C., Yao S.T., Antunes V.R. Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow. Purinergic Signal. 2013;9:337–349. doi: 10.1007/s11302-013-9352-9. PubMed DOI PMC

Barad Z., Jacob-Tomas S., Sobrero A., Lean G., Hicks A.I., Yang J., Choe K.Y., Prager-Khoutorsky M. Unique Organization of Actin Cytoskeleton in Magnocellular Vasopressin Neurons in Normal Conditions and in Response to Salt-Loading. eNeuro. 2020;7 doi: 10.1523/ENEURO.0351-19.2020. PubMed DOI PMC

Balapattabi K., Little J.T., Farmer G.E., Cunningham J.T. High salt loading increases brain derived neurotrophic factor in supraoptic vasopressin neurones. J. Neuroendocrinol. 2018;30:e12639. doi: 10.1111/jne.12639. PubMed DOI PMC

Martins Sa R.W., Theparambil S.M., Dos Santos K.M., Christie I.N., Marina N., Cardoso B.V., Hosford P.S., Antunes V.R. Salt-loading promotes extracellular ATP release mediated by glial cells in the hypothalamic paraventricular nucleus of rats. Mol. Cell Neurosci. 2023;124:103806. doi: 10.1016/j.mcn.2022.103806. PubMed DOI

Haam J., Halmos K.C., Di S., Tasker J.G. Nutritional state-dependent ghrelin activation of vasopressin neurons via retrograde trans-neuronal-glial stimulation of excitatory GABA circuits. J. Neurosci. 2014;34:6201–6213. doi: 10.1523/JNEUROSCI.3178-13.2014. PubMed DOI PMC

Wei B., Cheng G., Bi Q., Lu C., Sun Q., Li L., Chen N., Hu M., Lu H., Xu X., et al. Microglia in the hypothalamic paraventricular nucleus sense hemodynamic disturbance and promote sympathetic excitation in hypertension. Immunity. 2024;57:2030–2042. doi: 10.1016/j.immuni.2024.07.011. PubMed DOI

Kanjhan R., Housley G.D., Burton L.D., Christie D.L., Kippenberger A., Thorne P.R., Luo L., Ryan A.F. Distribution of the P2X2 receptor subunit of the ATP-gated ion channels in the rat central nervous system. J. Comp. Neurol. 1999;407:11–32. doi: 10.1002/(SICI)1096-9861(19990428)407:1<11::AID-CNE2>3.0.CO;2-R. PubMed DOI

Lommen J., Detken J., Harr K., von Gall C., Ali A.A.H. Analysis of Spatial and Temporal Distribution of Purinergic P2 Receptors in the Mouse Hippocampus. Int. J. Mol. Sci. 2021;22:8078. doi: 10.3390/ijms22158078. PubMed DOI PMC

Cipolla-Neto J., Skorupa A.L., Ribeiro-Barbosa E.R., Bartol I., Mota S.R., Afeche S.C., Delagrange P., Guardiola-Lemaitre B., Canteras N.S. The role of the retrochiasmatic area in the control of pineal metabolism. Neuroendocrinology. 1999;69:97–104. doi: 10.1159/000054407. PubMed DOI

Yamazaki S., Ishida Y., Inouye S. Circadian rhythms of adenosine triphosphate contents in the suprachiasmatic nucleus, anterior hypothalamic area and caudate putamen of the rat—Negative correlation with electrical activity. Brain Res. 1994;664:237–240. doi: 10.1016/0006-8993(94)91978-X. PubMed DOI

Womac A.D., Burkeen J.F., Neuendorff N., Earnest D.J., Zoran M.J. Circadian rhythms of extracellular ATP accumulation in suprachiasmatic nucleus cells and cultured astrocytes. Eur. J. Neurosci. 2009;30:869–876. doi: 10.1111/j.1460-9568.2009.06874.x. PubMed DOI PMC

Hastings M.H., Maywood E.S., Brancaccio M. The Mammalian Circadian Timing System and the Suprachiasmatic Nucleus as Its Pacemaker. Biology. 2019;8:13. doi: 10.3390/biology8010013. PubMed DOI PMC

McArthur A.J., Hunt A.E., Gillette M.U. Melatonin action and signal transduction in the rat suprachiasmatic circadian clock: Activation of protein kinase C at dusk and dawn. Endocrinology. 1997;138:627–634. doi: 10.1210/endo.138.2.4925. PubMed DOI

Marpegan L., Swanstrom A.E., Chung K., Simon T., Haydon P.G., Khan S.K., Liu A.C., Herzog E.D., Beaule C. Circadian regulation of ATP release in astrocytes. J. Neurosci. 2011;31:8342–8350. doi: 10.1523/JNEUROSCI.6537-10.2011. PubMed DOI PMC

Burkeen J.F., Womac A.D., Earnest D.J., Zoran M.J. Mitochondrial calcium signaling mediates rhythmic extracellular ATP accumulation in suprachiasmatic nucleus astrocytes. J. Neurosci. 2011;31:8432–8440. doi: 10.1523/JNEUROSCI.6576-10.2011. PubMed DOI PMC

Dworak M., McCarley R.W., Kim T., Kalinchuk A.V., Basheer R. Sleep and brain energy levels: ATP changes during sleep. J. Neurosci. 2010;30:9007–9016. doi: 10.1523/JNEUROSCI.1423-10.2010. PubMed DOI PMC

Buell G., Collo G., Rassendren F. P2X receptors: An emerging channel family. Eur. J. Neurosci. 1996;8:2221–2228. doi: 10.1111/j.1460-9568.1996.tb00745.x. PubMed DOI

Terasawa E., Keen K.L., Grendell R.L., Golos T.G. Possible role of 5′-adenosine triphosphate in synchronization of Ca2+ oscillations in primate luteinizing hormone-releasing hormone neurons. Mol. Endocrinol. 2005;19:2736–2747. doi: 10.1210/me.2005-0034. PubMed DOI

Vastagh C., Rodolosse A., Solymosi N., Liposits Z. Altered Expression of Genes Encoding Neurotransmitter Receptors in GnRH Neurons of Proestrous Mice. Front. Cell Neurosci. 2016;10:230. doi: 10.3389/fncel.2016.00230. PubMed DOI PMC

Bjelobaba I., Nedeljkovic N., Subasic S., Lavrnja I., Pekovic S., Stojkov D., Rakic L., Stojiljkovic M. Immunolocalization of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) in the rat forebrain. Brain Res. 2006;1120:54–63. doi: 10.1016/j.brainres.2006.08.114. PubMed DOI

Inoue N., Hazim S., Tsuchida H., Dohi Y., Ishigaki R., Takahashi A., Otsuka Y., Yamada K., Uenoyama Y., Tsukamura H. Hindbrain Adenosine 5-Triphosphate (ATP)-Purinergic Signaling Triggers LH Surge and Ovulation via Activation of AVPV Kisspeptin Neurons in Rats. J. Neurosci. 2023;43:2140–2152. doi: 10.1523/JNEUROSCI.1496-22.2023. PubMed DOI PMC

Constantin S., Klenke U., Wray S. The calcium oscillator of GnRH-1 neurons is developmentally regulated. Endocrinology. 2010;151:3863–3873. doi: 10.1210/en.2010-0118. PubMed DOI PMC

Bosma M.M. Ion channel properties and episodic activity in isolated immortalized gonadotropin-releasing hormone (GnRH) neurons. J. Membr. Biol. 1993;136:85–96. doi: 10.1007/BF00241492. PubMed DOI

Koshimizu T., Tomic M., Koshimizu M., Stojilkovic S.S. Identification of amino acid residues contributing to desensitization of the P2X2 receptor channel. J. Biol. Chem. 1998;273:12853–12857. doi: 10.1074/jbc.273.21.12853. PubMed DOI

Barnea A., Cho G., Katz B.M. A putative role for extracellular, A.T.P. facilitation of 67copper uptake and of copper stimulation of the release of luteinizing hormone-releasing hormone from median eminence explants. Brain Res. 1991;541:93–97. doi: 10.1016/0006-8993(91)91079-G. PubMed DOI

Zsarnovszky A., Bartha T., Frenyo L.V., Diano S. NTPDases in the neuroendocrine hypothalamus: Possible energy regulators of the positive gonadotrophin feedback. Reprod. Biol. Endocrinol. 2009;7:63. doi: 10.1186/1477-7827-7-63. PubMed DOI PMC

He M.L., Gonzalez-Iglesias A.E., Tomic M., Stojilkovic S.S. Release and extracellular metabolism of ATP by ecto-nucleotidase eNTPDase 1-3 in hypothalamic and pituitary cells. Purinergic Signal. 2005;1:135–144. doi: 10.1007/s11302-005-6208-y. PubMed DOI PMC

Allen-Worthington K., Xie J., Brown J.L., Edmunson A.M., Dowling A., Navratil A.M., Scavelli K., Yoon H., Kim D.G., Bynoe M.S., et al. The F0F1 ATP Synthase Complex Localizes to Membrane Rafts in Gonadotrope Cells. Mol. Endocrinol. 2016;30:996–1011. doi: 10.1210/me.2015-1324. PubMed DOI PMC

Chen Z.P., Kratzmeier M., Levy A., McArdle C.A., Poch A., Day A., Mukhopadhyay A.K., Lightman S.L. Evidence for a role of pituitary ATP receptors in the regulation of pituitary function. Proc. Natl. Acad. Sci. USA. 1995;92:5219–5223. doi: 10.1073/pnas.92.11.5219. PubMed DOI PMC

Tomic M., Jobin R.M., Vergara L.A., Stojilkovic S.S. Expression of purinergic receptor channels and their role in calcium signaling and hormone release in pituitary gonadotrophs. Integration of P2 channels in plasma membrane- and endoplasmic reticulum-derived calcium oscillations. J. Biol. Chem. 1996;271:21200–21208. doi: 10.1074/jbc.271.35.21200. PubMed DOI

Zemkova H., Balik A., Jiang Y., Kretschmannova K., Stojilkovic S.S. Roles of purinergic P2X receptors as pacemaking channels and modulators of calcium-mobilizing pathway in pituitary gonadotrophs. Mol. Endocrinol. 2006;20:1423–1436. doi: 10.1210/me.2005-0508. PubMed DOI

Gourine A.V., Melenchuk E.V., Poputnikov D.M., Gourine V.N., Spyer K.M. Involvement of purinergic signalling in central mechanisms of body temperature regulation in rats. Br. J. Pharmacol. 2002;135:2047–2055. doi: 10.1038/sj.bjp.0704679. PubMed DOI PMC

Klir J.J., McClellan J.L., Kluger M.J. Interleukin-1 beta causes the increase in anterior hypothalamic interleukin-6 during LPS-induced fever in rats. Pt 2Am. J. Physiol. 1994;266:R1845–R1848. doi: 10.1152/ajpregu.1994.266.6.R1845. PubMed DOI

Gourine A.V., Dale N., Gourine V.N., Spyer K.M. Fever in systemic inflammation: Roles of purines. Front. Biosci. 2004;9:1011–1022. doi: 10.2741/1301. PubMed DOI

Mehta V.B., Hart J., Wewers M.D. ATP-stimulated release of interleukin (IL)-1beta and IL-18 requires priming by lipopolysaccharide and is independent of caspase-1 cleavage. J. Biol. Chem. 2001;276:3820–3826. doi: 10.1074/jbc.M006814200. PubMed DOI

Hide I., Tanaka M., Inoue A., Nakajima K., Kohsaka S., Inoue K., Nakata Y. Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia. J. Neurochem. 2000;75:965–972. doi: 10.1046/j.1471-4159.2000.0750965.x. PubMed DOI

Gourine A.V., Poputnikov D.M., Zhernosek N., Melenchuk E.V., Gerstberger R., Spyer K.M., Gourine V.N. P2 receptor blockade attenuates fever and cytokine responses induced by lipopolysaccharide in rats. Br. J. Pharmacol. 2005;146:139–145. doi: 10.1038/sj.bjp.0706287. PubMed DOI PMC

Gourine A.V., Dale N., Llaudet E., Poputnikov D.M., Spyer K.M., Gourine V.N. Release of ATP in the central nervous system during systemic inflammation: Real-time measurement in the hypothalamus of conscious rabbits. Pt 1J. Physiol. 2007;585:305–316. doi: 10.1113/jphysiol.2007.143933. PubMed DOI PMC

Seidel B., Bigl M., Franke H., Kittner H., Kiess W., Illes P., Krugel U. Expression of purinergic receptors in the hypothalamus of the rat is modified by reduced food availability. Brain Res. 2006;1089:143–152. doi: 10.1016/j.brainres.2006.03.038. PubMed DOI

Steculorum S.M., Timper K., Engstrom Ruud L., Evers N., Paeger L., Bremser S., Kloppenburg P., Bruning J.C. Inhibition of P2Y6 Signaling in AgRP Neurons Reduces Food Intake and Improves Systemic Insulin Sensitivity in Obesity. Cell Rep. 2017;18:1587–1597. doi: 10.1016/j.celrep.2017.01.047. PubMed DOI

Pollatzek E., Hitzel N., Ott D., Raisl K., Reuter B., Gerstberger R. Functional expression of P2 purinoceptors in a primary neuroglial cell culture of the rat arcuate nucleus. Neuroscience. 2016;327:95–114. doi: 10.1016/j.neuroscience.2016.04.009. PubMed DOI

Wakamori M., Sorimachi M. Properties of native P2X receptors in large multipolar neurons dissociated from rat hypothalamic arcuate nucleus. Brain Res. 2004;1005:51–59. doi: 10.1016/j.brainres.2004.01.033. PubMed DOI

Steculorum S.M., Paeger L., Bremser S., Evers N., Hinze Y., Idzko M., Kloppenburg P., Bruning J.C. Hypothalamic UDP Increases in Obesity and Promotes Feeding via P2Y6-Dependent Activation of AgRP Neurons. Cell. 2015;162:1404–1417. doi: 10.1016/j.cell.2015.08.032. PubMed DOI

Sorimachi M., Ishibashi H., Moritoyo T., Akaike N. Excitatory effect of ATP on acutely dissociated ventromedial hypothalamic neurons of the rat. Neuroscience. 2001;105:393–401. doi: 10.1016/S0306-4522(01)00192-0. PubMed DOI

Kittner H., Franke H., Harsch J.I., El-Ashmawy I.M., Seidel B., Krugel U., Illes P. Enhanced food intake after stimulation of hypothalamic P2Y1 receptors in rats: Modulation of feeding behaviour by extracellular nucleotides. Eur. J. Neurosci. 2006;24:2049–2056. doi: 10.1111/j.1460-9568.2006.05071.x. PubMed DOI

Burnstock G., Gentile D. The involvement of purinergic signalling in obesity. Purinergic Signal. 2018;14:97–108. doi: 10.1007/s11302-018-9605-8. PubMed DOI PMC

Yu Y., He X., Zhang J., Tang C., Rong P. Transcutaneous auricular vagal nerve stimulation inhibits hypothalamic P2Y1R expression and attenuates weight gain without decreasing food intake in Zucker diabetic fatty rats. Sci. Prog. 2021;104:368504211009669. doi: 10.1177/00368504211009669. PubMed DOI PMC

Matsumoto N., Sorimachi M., Akaike N. Excitatory effects of ATP on rat dorsomedial hypothalamic neurons. Brain Res. 2004;1009:234–237. doi: 10.1016/j.brainres.2004.03.001. PubMed DOI

Kittner H., Franke H., Fischer W., Schultheis N., Krugel U., Illes P. Stimulation of P2Y1 receptors causes anxiolytic-like effects in the rat elevated plus-maze: Implications for the involvement of P2Y1 receptor-mediated nitric oxide production. Neuropsychopharmacology. 2003;28:435–444. doi: 10.1038/sj.npp.1300043. PubMed DOI

Vorobjev V.S., Sharonova I.N., Haas H.L., Sergeeva O.A. Expression and function of P2X purinoceptors in rat histaminergic neurons. Br. J. Pharmacol. 2003;138:1013–1019. doi: 10.1038/sj.bjp.0705144. PubMed DOI PMC

Vorobjev V.S., Sharonova I.N., Sergeeva O.A., Haas H.L. Modulation of ATP-induced currents by zinc in acutely isolated hypothalamic neurons of the rat. Br. J. Pharmacol. 2003;139:919–926. doi: 10.1038/sj.bjp.0705321. PubMed DOI PMC

Furukawa K., Ishibashi H., Akaike N. ATP-induced inward current in neurons freshly dissociated from the tuberomammillary nucleus. J. Neurophysiol. 1994;71:868–873. doi: 10.1152/jn.1994.71.3.868. PubMed DOI

Wollmann G., Acuna-Goycolea C., van den Pol A.N. Direct excitation of hypocretin/orexin cells by extracellular ATP at P2X receptors. J. Neurophysiol. 2005;94:2195–2206. doi: 10.1152/jn.00035.2005. PubMed DOI

Florenzano F., Viscomi M.T., Mercaldo V., Longone P., Bernardi G., Bagni C., Molinari M., Carrive P. P2X2R purinergic receptor subunit mRNA and protein are expressed by all hypothalamic hypocretin/orexin neurons. J. Comp. Neurol. 2006;498:58–67. doi: 10.1002/cne.21013. PubMed DOI

Jo Y.H., Role L.W. Coordinate release of ATP and GABA at in vitro synapses of lateral hypothalamic neurons. J. Neurosci. 2002;22:4794–4804. doi: 10.1523/JNEUROSCI.22-12-04794.2002. PubMed DOI PMC