title: Bidirectional roles of the brain 2-arachidonoyl-sn-glycerol in the centrally administered vasopressin-induced adrenomedullary outflow in rats.
abstract: Previously, we reported that intracerebroventricularly (i.c.v.) administered arginine-vasopressin evokes the secretion of noradrenaline and adrenaline from adrenal medulla through the brain phospholipase C- and diacylglycerol-mediated and cyclooxygenase-mediated mechanisms in rats. Diacylglycerol can be hydrolyzed by diacylglycerol lipase to 2-arachidonoyl-sn-glycerol, which may be further degradated by monoacylglycerol lipase to free arachidonic acid, a representative substrate of cyclooxygenase. Recently, 2-arachidonoyl-sn-glycerol has been recognized as a major endocannabinoid, which can modulate synaptic transmission in the brain. In the present experiment, therefore, we examined (1) a role of the brain 2-arachidonoyl-sn-glycerol as a precursor of arachidonic acid in the centrally administered vasopressin-induced elevation of plasma noradrenaline and adrenaline, and (2) a regulatory role of the brain 2-arachidonoyl-sn-glycerol as an endocannabinoid on the vasopressin-induced response, using urethane-anesthetized rats. The vasopressin (0.2 nmol/animal, i.c.v.)-induced elevation of plasma catecholamines was reduced by RHC-80267 (diacylglycerol lipase inhibitor) (1.3 and 2.6 micromol/animal, i.c.v.) and also reduced by MAFP (monoacylglycerol lipase inhibitor) (0.7 and 1.4 micromol/animal, i.c.v.). MAFP (1.4 micromol/animal, i.c.v.) also attenuated the 2-arachidonoyl-sn-glycerol (0.5 micromol/animal, i.c.v.)-induced elevation of plasma catecholamines. AM 251 (cannabinoid CB(1) receptor antagonist) (90 and 180 nmol/animal, i.c.v.) potentiated the vasopressin (0.2 nmol/animal, i.c.v.)-induced response, while AM 630 (cannabinoid CB(2) receptor antagonist) (198 and 793 nmol/animal, i.c.v.) was largely ineffective. In addition, WIN 55212-2 (cannabinoid CB receptor agonist) (188 and 470 nmol/animal, i.c.v.) dose-dependently reduced the vasopressin-induced response. These results suggest that the brain 2-arachidonoyl-sn-glycerol generated from diacylglycerol plays a role as a precursor of arachidonic acid in the centrally administered vasopressin-induced activation of the adrenomedullary outflow, and also negatively regulates the peptide-induced central response through the brain cannabinoid CB(1) receptors in rats.
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Kochi University, Nankoku, Kochi 783-8505, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokotani
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D048588:Benzoxazines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D002395:Catecholamines / Q000097:blood*; D003512:Cyclohexanones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D005989:Glycerides / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D063065:Organophosphonates / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D002395:Catecholamines; D003512:Cyclohexanones; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D007211:Indoles; D009025:Morpholines; D009281:Naphthalenes; D063065:Organophosphonates; D010880:Piperidines; D011720:Pyrazoles; C104810:methyl arachidonylfluorophosphonate; D001127:Arginine Vasopressin; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; C094503:glyceryl 2-arachidonate; C094023:iodopravadoline; D009638:Norepinephrine; D004837:Epinephrine