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

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• 作者：Takahiro Shimizu ; Kenjiro Tanaka ; Kumiko Nakamura ; Keisuke Taniuchi ; Kunihiko Yokotani
• 关键词：(± ; )-Epibatidine ; Brain ; Phospholipase C ; Diacylglycerol lipase ; Monoacylglycerol lipase ; Adrenal medulla
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 出版时间：15 September, 2012
• 年：2012
• 卷：691
• 期：1-3
• 页码：93-102
• 全文大小：912 K

文摘

We previously reported that intracerebroventricularly (i.c.v.) administered (¡À)-epibatidine (a potent agonist of nicotinic acetylcholine receptors) (1, 5 and 10 nmol/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, (¡À)-epibatidine (5 nmol/animal, i.c.v.)-induced elevation of plasma catecholamines was not influenced by pretreatment with mepacrine (phospholipase A₂ inhibitor) (1.1 and 2.2 ¦Ìmol/animal, i.c.v.), but was effectively reduced by pretreatment with U-73122 (1-[6-[[(17¦Â)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) (phospholipase C inhibitor) (10 and 30 nmol/animal, i.c.v.), RHC-80267 [1,6-bis(cyclohexyloximinocarbonylamino)hexane] (diacylglycerol lipase inhibitor) (1.3 and 2.6 ¦Ìmol/animal, i.c.v.), MAFP (methyl arachidonoyl fluorophosphonate) (monoacylglycerol lipase inhibitor) (0.7 and 1.4 ¦Ìmol/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 1.4 ¦Ìmol/animal, i.c.v.). Immunohistochemical studies demonstrated that (¡À)-epibatidine (10 nmol/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 (¡À)-epibatidine-induced activation of central adrenomedullary outflow in rats.