Brain phospholipase C, diacylglycerol lipase and monoacylglycerol lipase are involved in (±)-epibatidine-induced activation of central adrenomedullary outflow in rats.
Brain phospholipase C, diacylglycerol lipase and monoacylglycerol lipase are involved in (±)-epibatidine-induced activation of central adrenomedullary outflow in rats.
复制标题
脑磷脂酶 C、二酰甘油脂肪酶和单酰甘油脂肪酶参与 (±)-epibatidine 诱导的大鼠中枢肾上腺髓质流出物的激活。
DOI：
10.1016/j.ejphar.2012.07.017
复制
发表时间：
2012
影响因子：
5
通讯作者：
Takahiro Shimizu
中科院分区：
文献类型：
--
作者：
Tanaka K;Shimizu T;Yanagita T;Nemoto T;Nakamura K;Taniuchi K;Dimitriadis F;Yokotani K;Saito M;Takahiro Shimizu;Takahiro Shimizu
我们先前报道了脑室内(i.c.v.)给予(±)-表巴替丁(烟碱型乙酰胆碱受体的强效激动剂)(1、5和10nmol/只)可剂量依赖性地升高血浆去甲肾上腺素和肾上腺素水平，这种反应可被侧脑室注射减弱。给予吲哚美辛(环氧合酶抑制剂)，并被双侧肾上腺切除取消，表明作为环氧合酶底物的脑花生四烯酸参与了这种生物碱诱导的大鼠肾上腺髓质中儿茶酚胺的分泌。花生四烯酸主要通过磷脂酶A2的作用释放，但也通过磷脂酶C-、二酰甘油脂肪酶和单甘油脂肪酶介导的途径释放。在本研究中，(±)-表巴替丁(5nmoL/只，i.c.v)引起的血浆儿茶酚胺的升高不受预先给予甲帕克林(磷脂酶A2抑制剂)(1.1nmo1和2.2nmoL/只，i.c.v)的影响，但可被U-73122(1-[6-[[(17β)-3-methoxyestra-1，3，5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2，5-dione)(磷脂酶C抑制剂)(10和30nmoL/只)有效地降低。Rhc-80267[1，6-bis(cyclohexyloximinocarbonylamino)hexane](1.3和2.6μ/动物，i.c.V.)，MAFP(花生四烯酸甲酯)(单酰甘油脂肪酶抑制剂)(0.7和1.4μ/动物，i.c.v.)或JZL184[4-硝基苯基4-(dibenzo[d][1，3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate](选择性单酰基甘油脂肪酶抑制剂)(0.7Mol/μ/动物，i.c.v.)。免疫组织化学研究表明，(±)-epbatidine(10nmol/只，i.c.v.)激活大鼠下丘脑室旁核中表达单酰甘油脂肪酶的脊髓投射神经元，下丘脑室旁核是中枢交感神经-肾上腺髓质流出的控制中心。综上所述，脑磷脂酶C、二酰甘油脂酶和单甘油脂酶介导的途径似乎参与了中枢应用(±)-表巴替丁引起的中枢肾上腺髓质流出的激活。
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 A2inhibitor) (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.