title: Stimulatory and inhibitory roles of brain 2-arachidonoylglycerol in bombesin-induced central activation of adrenomedullary outflow in rats.
abstract: 2-Arachidonoylglycerol (2-AG) is recognized as a potent endocannabinoid, which reduces synaptic transmission through cannabinoid CB(1) receptors, and is hydrolyzed by monoacylglycerol lipase (MGL) to arachidonic acid (AA), a cyclooxygenase substrate. We already reported that centrally administered MGL and cyclooxygenase inhibitors each reduced the intracerebroventricularly (i.c.v.) administered bombesin-induced secretion of adrenal catecholamines, while a centrally administered CB(1)-antagonist potentiated the response, indirectly suggesting bidirectional roles of brain 2-AG (stimulatory and inhibitory roles) in the bombesin-induced response. In the present study, we separately examined these bidirectional roles using 2-AG and 2-AG ether (2-AG-E) (stable 2-AG analog for MGL) in rats. 2-AG (0.5 μmol/animal, i.c.v.), but not 2-AG-E (0.5 μmol/animal, i.c.v.), elevated basal plasma catecholamines with JZL184 (MGL inhibitor)- and indomethacin (cyclooxygenase inhibitor)-sensitive brain mechanisms. 2-AG-E (0.1 μmol/animal, i.c.v.) effectively reduced the bombesin (1 nmol/animal, i.c.v.)-induced elevation of plasma catecholamines with rimonabant (CB(1) antagonist)-sensitive brain mechanisms. Immunohistochemical studies demonstrated the bombesin-induced activation of diacylglycerol lipase α (2-AG-producing enzyme)-positive spinally projecting neurons in the hypothalamic paraventricular nucleus, a control center of central adrenomedullary outflow. These results directly indicate bidirectional roles of brain 2-AG, a stimulatory role as an AA precursor and an inhibitory role as an endocannabinoid, in the bombesin-induced central adrenomedullary outflow in rats.
authors: Department of Pharmacology, School of Medicine, Kochi University, Kochi, Japan. shimizu@kochi-u.ac.jp
authors: Takahiro
authors: T
authors: Shimizu
authors: Kenjiro
authors: K
authors: Tanaka
authors: Kunihiko
authors: K
authors: Yokotani
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D052117:Benzodioxoles / Q000008:administration & dosage / Q000494:pharmacology; D001839:Bombesin / Q000008:administration & dosage / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D063388:Endocannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D005989:Glycerides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000819:agonists* / Q000037:antagonists & inhibitors; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D000077285:Rimonabant
chemical_list: D001095:Arachidonic Acids; D052117:Benzodioxoles; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002395:Catecholamines; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D005989:Glycerides; C534333:JZL 184; D018377:Neurotransmitter Agents; D010880:Piperidines; D011720:Pyrazoles; C424442:noladin ether; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases; D008071:Lipoprotein Lipase; D001839:Bombesin; D000077285:Rimonabant; D007213:Indomethacin