OBJECTIVE: Overview of current knowledge in the field of the endocannabinoid system with emphasis on the relationships between endocannabinoids and exocannabinoids. The endocannabinoid system consists of cannabinoid receptors 1 and 2, ligands of these receptors, especially two classical; endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoyl-glycerol. Transport systems that ensure the entry of endocannabinoids into cells, where they are degraded by fatty acid amide hydrolase or monoacylglycerol lipase. The endocannabinoid system is a signaling pathway for the regulation of a number of physiological or pathological conditions. So far, it is one of the less explored ways of regulation, as evidenced by the recent explosive increase in the number of published works. Dysregulation of endocannabinoid systems is a possible cause of many diseases. It can occur both in the genetic polymorphism of its individual components, but also in therapy with certain drugs or natural substances, typically cannabinoids. Due to the wide overlap of the regulation of physiological functions by the endocannabinoid system, a considerable number of drugs are being developed, the aim of which is to correct the dysregulation of the endocannabinoid system. CONCLUSION: The endocannabinoid system is one of the most important regulatory systems with a very broad intervention in physiological and pathological conditions. The resulting specific regulations intersect the interplay of many enzymes involved in the production and degradation of endocannabinoids, transport systems involved in the entry of endocannabinoids into cells, cannabinoid receptors and exogenous cannabinoids, or natural substances acting at various sites in the endocannabinoid system. Knowledge in this area can contribute to improving health care and increasing the safety of its provision.

• Klíčová slova
• 2-arachidoyl glycerol, Cannabinoids, Endocannabinoids, anandamide, cannabinoid receptor, fatty acid amide hydrolases, fatty acid binding proteins, lipase for monoacylglycerols,
• MeSH
• endokanabinoidy * MeSH
• kanabinoidy * MeSH
• lidé MeSH
• receptory kanabinoidní MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endokanabinoidy * MeSH
• kanabinoidy * MeSH
• receptory kanabinoidní MeSH

Progress in understanding the molecular mechanisms of cannabis action was made after discovery of cannabinoid receptors in the brain and the finding of endogenous metabolites with affinity to them. Activation of cannabinoid receptors on synaptic terminals results in regulation of ion channels, neurotransmitter release and synaptic plasticity. Neuromodulation of synapses by the cannabinoids is proving to have a wide range of functional effects, making them potential targets as medical preparations in a variety of illnesses, including some mental disorders and neurodegenerative illnesses. Cannabis contains a large amount of substances with affinity for the cannabinoid receptors. The endocannabinoids are a family of lipid neurotransmitters that engage the same membrane receptors targeted by tetrahydrocannabinol and that mediate retrograde signal from postsynaptic neurons to presynaptic ones. Discovery of endogenous cannabinoids and studies of the physiological functions of the cannabinoid system in the brain and body are producing a number of important findings about the role of membrane lipids and fatty acids in nerve signal transduction. Plant, endogenous and synthetic cannabinoids are using in these studies. The role of lipid membranes in the cannabinoid system follows from the fact that the source and supply of endogenous cannabinoids are derived from arachidonic acid, an important membrane constituent. The study of structure-activity relationships of molecules which influence the cannabinoid system in the brain and body is crucial in search of medical preparations with the therapeutic effects of the phytocannabinoids without the negative effects on cognitive function attributed to cannabis.

• MeSH
• Cannabis chemie   MeSH
• endokanabinoidy * MeSH
• kanabinoidy chemie   farmakologie   MeSH
• léčivé rostliny chemie   MeSH
• lidé MeSH
• modulátory kanabinoidních receptorů metabolismus   MeSH
• receptory kanabinoidní účinky léků   metabolismus   MeSH
• signální transdukce fyziologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• endokanabinoidy * MeSH
• kanabinoidy MeSH
• modulátory kanabinoidních receptorů MeSH
• receptory kanabinoidní MeSH

OBJECTIVE: In this paper, we summarize the role of the endocannabinoid system in relation to pregnancy and childbirth and its potential for dia-gnosis of preterm birth. METHODS: Review of articles in peer-reviewed journals using the PubMed database. RESULTS: Endocannabinoid system plays a significant role in embryo development, transport and implantation as well as in placentation. It consists of numerous endogenous ligands; however, in relation to pregnancy there are mainly two studied representatives: anandamide and 2-arachidonoylglycerol. There is increasing evidence, in addition to early pregnancy events, that anandamide plays a regulatory role in pregnancy maintenance and the timing of labour. The activity of anandamide depends on its metabolic pathway and the enzymatic activity that ensures its conversion. Ultimately, changes in anandamide concentration lead to increased production of prostaglandins or prostamides, with inverse effects on pregnancy. The abuse of exogenous cannabinoids in pregnancy has substantial impact on the unborn child in many ways and may result in detrimental effects including preterm birth. CONCLUSION: Measuring anandamide concentration and the prostaglandin to prostamide ratio could be a useful tool in assessing the risk of preterm birth.

• Klíčová slova
• childbirth, endocannabinoid system, labour, pregnancy,
• MeSH
• dospělí MeSH
• endokanabinoidy * MeSH
• implantace embrya MeSH
• lidé MeSH
• novorozenec MeSH
• předčasný porod * MeSH
• prostaglandiny MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endokanabinoidy * MeSH
• prostaglandiny MeSH

Freshwater bryozoan Pectinatella magnifica was collected from a sand pit (South Bohemia). The total lipids after extraction from lyophilized bryozoans were analyzed using high-performance liquid chromatography/high-resolution negative tandem electrospray mass spectrometry. A total of 19 lipid classes were identified, including N-acyl-substituted phospholipids, that is, N-acylphosphatidylethanolamine and N-acylphosphatidylserine in their plasmenyl forms. Based on gas chromatography/mass spectrometry of 3-pyridylcarbonyl (picolinyl) esters, a very unusual fatty acid was identified, namely 24:7n-3 (all-cis-3,6,9,12,15,18,21-tetracosaheptaenoic acid). The presence of polyunsaturated fatty acids in individual classes is very specific: arachidonic and eicosapentaenoic acids being predominantly bound as amides in N-acyl phospholipids, that is, diacyl-N-acylphosphatidylethanolamines (NAPtdEtn), plasmenyl-N-acylphosphatidyl ethanolamines (PlsNAPtdEtn), diacyl-N-acylphosphatidylserines (NAPtdSer), and plasmenyl-N-acylphosphatidylserines (PlsNAPtdSer). While 24:6n-3 was identified in the sn-2 position of several phospholipids, 24:7n-3 was identified in only two plasmalogens, that is, PlsNAPtdEtn and PlsNAPtdSer. Thanks to the tandem mass spectrometry, we managed to identify the position of all acyl groups in both diacyl- and also in alkenyl-acyl-(plasmenyl) molecular species of N-acylphospholipids. The identification of the molecular species of N-acyl-substituted phosphatidylethanolamine and phosphatidylserine, including their plasmalogen forms, in the freshwater bryozoan P. magnifica has enabled the identification of endogenous cannabinoid precursors.

• Klíčová slova
• Endocannabinoids, Freshwater bryozoan, Lipidomics, Liquid chromatography/tandem high-resolution electrospray mass spectrometry, N-acylphosphatidylethanolamines, Pectinatella magnifica,
• MeSH
• Bryozoa chemie   MeSH
• endokanabinoidy analýza   chemie   MeSH
• sladká voda MeSH
• tandemová hmotnostní spektrometrie MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endokanabinoidy MeSH

RATIONALE AND OBJECTIVES: In addition to dopamine, endocannabinoids are thought to participate in neural reward mechanisms of opioids. Number of recent studies suggests crucial involvement of ghrelin in some addictive drugs effects. Our previous results showed that ghrelin participates in morphine-induced changes in the mesolimbic dopaminergic system associated with reward processing. The goal of the present study was to test whether the growth hormone secretagogue receptor (GHS-R1A) antagonist JMV2959 was able to influence morphine-induced effects on anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) in the nucleus accumbens shell (NACSh). METHODS: We used in vivo microdialysis to determine changes in levels of AEA and 2-AG in the NACSh in rats following (i) an acute morphine dose (5, 10 mg/kg s.c.) with and without JMV2959 pretreatment (3, 6 mg/kg i.p.) or (ii) a morphine challenge dose (5 mg/kg s.c.) with and without JMV2959 (3, 6 mg/kg i.p.) pretreatment, administered during abstinence following repeated doses of morphine (5 days, 10-40 mg/kg). Co-administration of ghrelin (40 ug/kg i.p.) was used to verify the ghrelin mechanisms involvement. RESULTS: Pretreatment with JMV2959 significantly and dose-dependently reversed morphine-induced anandamide increases in the NACSh in both the acute and longer-term models, resulting in a significant AEA decrease. JMV2959 significantly intensified acute morphine-induced decreases in accumbens 2-AG levels and attenuated morphine challenge-induced 2-AG decreases. JMV2959 pretreatment significantly reduced concurrent morphine challenge-induced behavioral sensitization. JMV2959 pretreatment effects were abolished by co-administration of ghrelin. CONCLUSIONS: Our results indicate significant involvement of ghrelin signaling in morphine-induced endocannabinoid changes in the NACSh.

• Klíčová slova
• 2-Arachidonoylglycerol, Acute, Anandamide, Challenge during abstinence, Endocannabinoids, Ghrelin, Microdialysis, Morphine, Neural reward system, Nucleus accumbens shell, Stereotyped behavior,
• MeSH
• endokanabinoidy metabolismus   fyziologie   MeSH
• extracelulární prostor účinky léků   metabolismus   MeSH
• ghrelin fyziologie   MeSH
• glyceridy metabolismus   MeSH
• glycin analogy a deriváty   farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyseliny arachidonové metabolismus   MeSH
• morfin farmakologie   MeSH
• narkotika farmakologie   MeSH
• nucleus accumbens účinky léků   metabolismus   MeSH
• polynenasycené alkamidy metabolismus   MeSH
• potkani Wistar MeSH
• receptory ghrelinu antagonisté a inhibitory   MeSH
• receptory somatotropinu antagonisté a inhibitory   MeSH
• stereotypní chování účinky léků   MeSH
• triazoly farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anandamide MeSH Prohlížeč
• endokanabinoidy MeSH
• ghrelin MeSH
• glyceridy MeSH
• glyceryl 2-arachidonate MeSH Prohlížeč
• glycin MeSH
• kyseliny arachidonové MeSH
• morfin MeSH
• N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Prohlížeč
• narkotika MeSH
• polynenasycené alkamidy MeSH
• receptory ghrelinu MeSH
• receptory somatotropinu MeSH
• triazoly MeSH

Light entrains the master circadian clock in the suprachiasmatic nucleus (SCN) predominantly through glutamatergic signaling via NMDA receptors. The magnitude and the direction of resulting phase shifts depend on timing of the photic stimulus. Previous reports based on behavioral and electrophysiological data suggested that endocannabinoids (EC) might reduce the ability of the SCN clock to respond to light. However, there is little direct evidence for the involvement of EC in entrainment of the rhythmic clock gene expression in the SCN. We have used luminescence recording of cultured SCN slices from mPer2 Luc mice to construct a complete phase response curve (PRC) for NMDA receptor activation. The results demonstrated that NMDA administration phase-shifts the PER2 rhythm in a time-specific manner. A stable "singularity," in the course of which the clock seemingly stops while the overall phase is caught between delays and advances, can occur in response to NMDA at a narrow interval during the PER2 level decrease. NMDA-induced phase delays were affected neither by the agonist (WIN 55,212-2 mesylate) nor by the antagonist (rimonabant hydrochloride) of EC receptors. However, the agonist significantly reduced the NMDA-induced phase advance of the clock, while the antagonist enhanced the phase advance, causing a shift in the sensitivity window of the SCN to NMDA. The modulation of EC signaling in the SCN had no effect by itself on the phase of the PER2 rhythm. The results provide evidence for a modulatory role of EC in photic entrainment of the circadian clock in the SCN.

• Klíčová slova
• NMDA, PER2::LUC, circadian, endocannabinoids, entrainment, glutamate receptor, phase response curve, suprachiasmatic nucleus,
• Publikační typ
• časopisecké články MeSH

The endocannabinoid/CB1R system as well as the central ghrelin signalling with its growth hormone secretagogoue receptors (GHS-R1A) are importantly involved in food intake and reward/reinforcement processing and show distinct overlaps in distribution within the relevant brain regions including the hypothalamus (food intake), the ventral tegmental area (VTA) and the nucleus accumbens (NAC) (reward/reinforcement). The significant mutual interaction between these systems in food intake has been documented; however, the possible role of ghrelin/GHS-R1A in the cannabinoid reinforcement effects and addiction remain unclear. Therefore, the principal aim of the present study was to investigate whether pretreatment with GHS-R1A antagonist/JMV2959 could reduce the CB1R agonist/WIN55,212-2-induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. The synthetic aminoalklylindol cannabinoid WIN55,212-2 administration into the posterior VTA induced significant accumbens dopamine release, which was significantly reduced by the 3 mg/kg i.p. JMV2959 pretreatment. Simultaneously, the cannabinoid-increased accumbens dopamine metabolic turnover was significantly augmented by the JMV2959 pretreament. The intracerebral WIN55,212-2 administration also increased the endocannabinoid arachidonoylethanolamide/anandamide and the 2-arachidonoylglycerol/2-AG extracellular levels in the NACSh, which was moderately but significantly attenuated by the JMV2959 pretreatment. Moreover, the cannabinoid-induced decrease in accumbens γ-aminobutyric acid/gamma-aminobutyric acid levels was reversed by the JMV2959 pretreatment. The behavioural study in the LABORAS cage showed that 3 mg/kg JMV2959 pretreatment also significantly reduced the systemic WIN55,212-2-induced behavioural stimulation. Our results demonstrate that the ghrelin/GHS-R1A system significantly participates in the rewarding/reinforcing effects of the cannabinoid/CB1 agonist that are involved in cannabinoid addiction processing.

• Klíčová slova
• 2-arachidonoylglycerol/2-AG, GABA, addiction, anandamide/AEA, dopamine, dopamine metabolism, endocannabinoids, ghrelin/GHS-R1A, nucleus accumbens shell microdialysis, synthetic cannabinoid WIN55,212-2,
• MeSH
• benzoxaziny aplikace a dávkování   MeSH
• dopamin metabolismus   MeSH
• endokanabinoidy metabolismus   MeSH
• GABA metabolismus   MeSH
• ghrelin metabolismus   MeSH
• glyceridy metabolismus   MeSH
• glycin aplikace a dávkování   analogy a deriváty   MeSH
• kyseliny arachidonové metabolismus   MeSH
• morfoliny aplikace a dávkování   MeSH
• naftaleny aplikace a dávkování   MeSH
• nucleus accumbens účinky léků   metabolismus   MeSH
• polynenasycené alkamidy metabolismus   MeSH
• potkani Wistar MeSH
• preklinické hodnocení léčiv MeSH
• triazoly aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone MeSH Prohlížeč
• anandamide MeSH Prohlížeč
• benzoxaziny MeSH
• dopamin MeSH
• endokanabinoidy MeSH
• GABA MeSH
• ghrelin MeSH
• glyceridy MeSH
• glyceryl 2-arachidonate MeSH Prohlížeč
• glycin MeSH
• kyseliny arachidonové MeSH
• morfoliny MeSH
• N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Prohlížeč
• naftaleny MeSH
• polynenasycené alkamidy MeSH
• triazoly MeSH

Suprachiasmatic nucleus (SCN) of the hypothalamus is the master clock that drives circadian rhythms in physiology and behavior and adjusts their timing to external cues. Neurotransmitter glutamate and glutamatergic receptors sensitive to N-methyl-d-aspartate (NMDA) play a dual role in the SCN by coupling astrocytic and neuronal single cell oscillators and by resetting their phase in response to light. Recent reports suggested that signaling by endogenous cannabinoids (ECs) participates in both of these functions. We have previously shown that ECs, such as 2-arachidonoylglycerol (2-AG), act via CB1 receptors to affect the SCN response to light-mimicking NMDA stimulus in a time-dependent manner. We hypothesized that this ability is linked to the circadian regulation of EC signaling. We demonstrate that circadian clock in the rat SCN regulates expression of 2-AG transport, synthesis and degradation enzymes as well as its receptors. Inhibition of the major 2-AG synthesis enzyme, diacylglycerol lipase, enhanced the phase delay and lowered the amplitude of explanted SCN rhythm in response to NMDAR activation. Using microscopic PER2 bioluminescence imaging, we visualized how individual single cell oscillators in different parts of the SCN respond to the DAGL inhibition/NMDAR activation and shape response of the whole pacemaker. Additionally, we present strong evidence that the zero amplitude behavior of the SCN in response to single NMDA stimulus in the middle of subjective night is the result of a loss of rhythm in individual SCN cells. The paper provides new insights into the modulatory role of endocannabinoid signaling during the light entrainment of the SCN.

• Klíčová slova
• Circadian, Endocannabinoids, N-Methyl-d-aspartate, PER2::LUC, Phase response curve, Suprachiasmatic nucleus,
• MeSH
• agonisté excitačních aminokyselin farmakologie   MeSH
• cirkadiánní rytmus účinky léků   fyziologie   MeSH
• endokanabinoidy fyziologie   MeSH
• krysa rodu Rattus MeSH
• lipoproteinlipasa antagonisté a inhibitory   metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• N-methylaspartát farmakologie   MeSH
• nucleus suprachiasmaticus cytologie   účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• agonisté excitačních aminokyselin MeSH
• endokanabinoidy MeSH
• lipoproteinlipasa MeSH
• N-methylaspartát MeSH

The endocannabinoid system is an endogenous signaling system that plays a role in the regulation of energy homeostasis and lipid and glucose metabolism-all of which can influence cardiometabolic risk. The endocannabinoid system is normally a silent physiologic system that becomes transiently activated, that is, only when needed. Endocannabinoids may also be secreted by the endothelium. Accordingly, there has been interest in the interactions between endocannabinoids and blood cells. There is certainly evidence that endocannabinoids, especially 2-arachidonoylglycerol (2-AG), may promote platelet activation, indicating that they may participace in regulation of thrombosis and inflammation. Platelets are involved both in the metabolism and release of endocannabinoids, and so it is possible that their circulating levels may be regulated by platelets. 2-AG can be considered a new physiologic platelet agonist able to induce full platelet activation and aggregation with a non-CB1/CB2 receptor-mediated mechanism. Not only may endocannabinoids regulate platelet function and possibly lead to thrombogenesis, but they may also influence haematopoesis.

• MeSH
• agregace trombocytů fyziologie   MeSH
• aktivace trombocytů fyziologie   MeSH
• endokanabinoidy * MeSH
• glyceridy fyziologie   MeSH
• kyseliny arachidonové fyziologie   MeSH
• lidé MeSH
• modulátory kanabinoidních receptorů fyziologie   MeSH
• trombocyty fyziologie   MeSH
• trombóza patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• endokanabinoidy * MeSH
• glyceridy MeSH
• glyceryl 2-arachidonate MeSH Prohlížeč
• kyseliny arachidonové MeSH
• modulátory kanabinoidních receptorů MeSH

The endocannabinoid system (ECS), which is composed of the cannabinoid receptors types 1 and 2 (CB1 and CB2) for marijuana's psychoactive ingredient Δ9-tetrahydrocannabinol (Δ9-THC), the endogenous ligands (AEA and 2-AG) and the enzymatic systems involved in their biosynthesis and degradation, recently emerged as important modulator of emotional and non-emotional behaviors. For centuries, in addition to its recreational actions, several contradictory claims regarding the effects of Cannabis use in sexual functioning and behavior (e.g. aphrodisiac vs anti-aphrodisiac) of both sexes have been accumulated. The identification of Δ9-THC and later on, the discovery of the ECS have opened a potential therapeutic target for sexual dysfunctions, given the partial efficacy of current pharmacological treatment. In agreement with the bidirectional modulation induced by cannabinoids on several behavioral responses, the endogenous cannabinoid AEA elicited biphasic effects on sexual behavior as well. The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of several aspects of sexuality in preclinical and human studies, highlighting their therapeutic potential.

• Klíčová slova
• Cannabinoid CB1 receptor, Endocannabinoids, Sexual behavior, Δ(9)-THC,
• MeSH
• endokanabinoidy metabolismus   MeSH
• kanabinoidy metabolismus   MeSH
• lidé MeSH
• modulátory kanabinoidních receptorů metabolismus   MeSH
• receptory kanabinoidní metabolismus   MeSH
• sexuální chování fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• endokanabinoidy MeSH
• kanabinoidy MeSH
• modulátory kanabinoidních receptorů MeSH
• receptory kanabinoidní MeSH