Brain phospholipase C, diacylglycerol lipase and monoacylglycerol lipase are involved in (±)-epibatidine-induced activation of central adrenomedullary outflow in rats

• Published in: European journal of pharmacology 2012-09, Vol.691 (1-3), p.93-102
• Main Authors: Shimizu, Takahiro, Tanaka, Kenjiro, Nakamura, Kumiko, Taniuchi, Keisuke, Yokotani, Kunihiko
• Format: Article
• Language: English
• Subjects: (±)-Epibatidine; acylglycerol lipase; Adrenal medulla; Adrenal Medulla - drug effects; Adrenal Medulla - secretion; agonists; Animals; arachidonic acid; Arachidonic Acids - pharmacology; Benzodioxoles - pharmacology; Brain; Brain - drug effects; Brain - enzymology; Bridged Bicyclo Compounds, Heterocyclic - administration & dosage; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Catecholamines - blood; Catecholamines - secretion; cholinergic receptors; Cyclohexanones - pharmacology; Diacylglycerol lipase; epinephrine; Esterases - metabolism; Estrenes - pharmacology; hexane; immunohistochemistry; indomethacin; lipoprotein lipase; Lipoprotein Lipase - metabolism; Male; Monoacylglycerol lipase; Monoacylglycerol Lipases - metabolism; neurons; Neurons - drug effects; Neurons - enzymology; Nicotinic Agonists - administration & dosage; Nicotinic Agonists - pharmacology; norepinephrine; Organophosphonates - pharmacology; paraventricular hypothalamic nucleus; Paraventricular Hypothalamic Nucleus - cytology; Phospholipase C; Piperidines - pharmacology; prostaglandin synthase; Pyridines - administration & dosage; Pyridines - pharmacology; Pyrrolidinones - pharmacology; quinacrine; Rats; Rats, Wistar; secretion; Type C Phospholipases - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.07.017

We previously reported that intracerebroventricularly (i.c.v.) administered (±)-epibatidine (a potent agonist of nicotinic acetylcholine receptors) (1, 5 and 10nmol/animal) dose-dependently elevated plasma levels of noradrenaline and adrenaline and that this response was reduced by i.c.v. administered indomethacin (cyclooxygenase inhibitor) and abolished by bilateral adrenalectomy, indicating the involvement of brain arachidonic acid, as a substrate of cyclooxygenase, in this alkaloid-induced secretion of both catecholamines from the adrenal medulla in rats. Arachidonic acid is mainly released by the action of phospholipase A2, but is also released by a phospholipase C-, diacylglycerol lipase- and monoacylglycerol lipase-mediated pathway. In the present study, (±)-epibatidine (5nmol/animal, i.c.v.)-induced elevation of plasma catecholamines was not influenced by pretreatment with mepacrine (phospholipase A2 inhibitor) (1.1 and 2.2μmol/animal, i.c.v.), but was effectively reduced by pretreatment with U-73122 (1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) (phospholipase C inhibitor) (10 and 30nmol/animal, i.c.v.), RHC-80267 [1,6-bis(cyclohexyloximinocarbonylamino)hexane] (diacylglycerol lipase inhibitor) (1.3 and 2.6μmol/animal, i.c.v.), MAFP (methyl arachidonoyl fluorophosphonate) (monoacylglycerol lipase inhibitor) (0.7 and 1.4μmol/animal, i.c.v.) or JZL184 [4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate] (selective monoacylglycerol lipase inhibitor) (0.7 and 1.4μmol/animal, i.c.v.). Immunohistochemical studies demonstrated that (±)-epibatidine (10nmol/animal, i.c.v.) activates spinally projecting neurons expressing monoacylglycerol lipase in the rat hypothalamic paraventricular nucleus, a control center of central sympatho-adrenomedullary outflow. Taken together, the brain phospholipase C-, diacylglycerol lipase- and monoacylglycerol lipase-mediated pathway seems to be involved in the centrally administered (±)-epibatidine-induced activation of central adrenomedullary outflow in rats.