Shimizu Takahiro, Okada Shoshiro, Yamaguchi-Shima Naoko, Yokotani Kunihiko
Department of Neuropharmacology, Program of Neural Integration, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.
Eur J Pharmacol. 2004 Sep 19;499(1-2):99-105. doi: 10.1016/j.ejphar.2004.07.087.
Recently, we reported that intracerebroventricularly (i.c.v.) administered arginine-vasopressin evokes the release of noradrenaline and adrenaline from adrenal medulla by brain thromboxane A2-mediated mechanisms in rats. These results suggest the involvement of brain arachidonic acid in the vasopressin-induced activation of the central adrenomedullary outflow. Arachidonic acid is released mainly by two pathways: phospholipase A2 (PLA2)-dependent pathway; phospholipase C (PLC)- and diacylglycerol lipase-dependent pathway. In the present study, therefore, we attempted to identify which pathway is involved in the vasopressin-induced release of both catecholamines from adrenal medulla using urethane-anesthetized rats. Vasopressin (0.2 nmol/animal, i.c.v.)-induced elevation of plasma noradrenaline and adrenaline was dose-dependently reduced by neomycin [0.28 and 0.55 micromol (250 and 500 microg)/animal, i.c.v.] and 1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) [5 and 10 nmol (2.3 and 4.6 microg)/animal, i.c.v.] (inhibitors of PLC), and also by 1,6-bis(cyclohexyloximinocarbonylamino)hexane (RHC-80267) [1.3 and 2.6 micromol (500 and 1000 microg)/animal, i.c.v.] (an inhibitor of diacylglycerol lipase). On the other hand, mepacrine [1.1 and 2.2 micromol (500 and 1000 microg)/animal, i.c.v.] (an inhibitor of PLA2) was largely ineffective on the vasopressin-induced elevation of plasma catecholamines. These results suggest that vasopressin evokes the release of noradrenaline and adrenaline from adrenal medulla by the brain PLC- and diacylglycerol lipase-dependent mechanisms in rats.
最近,我们报道了在大鼠中,脑室内(i.c.v.)注射精氨酸加压素通过脑血栓素A2介导的机制,引起肾上腺髓质去甲肾上腺素和肾上腺素的释放。这些结果表明,脑花生四烯酸参与了加压素诱导的中枢肾上腺髓质传出神经激活。花生四烯酸主要通过两条途径释放:磷脂酶A2(PLA2)依赖性途径;磷脂酶C(PLC)和二酰基甘油脂肪酶依赖性途径。因此,在本研究中,我们试图使用乌拉坦麻醉的大鼠来确定哪种途径参与了加压素诱导的肾上腺髓质中两种儿茶酚胺的释放。新霉素[0.28和0.55微摩尔(250和500微克)/动物,i.c.v.]和1-[6-[[(17β)-3-甲氧基雌甾-1,3,5(10)-三烯-17-基]氨基]己基]-1H-吡咯-2,5-二酮(U-73122)[5和10纳摩尔(2.3和4.6微克)/动物,i.c.v.](PLC抑制剂)以及1,6-双(环己基氧代羰基氨基)己烷(RHC-80267)[1.3和2.6微摩尔(500和1000微克)/动物,i.c.v.](二酰基甘油脂肪酶抑制剂)剂量依赖性地降低了加压素(0.2纳摩尔/动物,i.c.v.)诱导的血浆去甲肾上腺素和肾上腺素升高。另一方面,米帕林[1.1和2.2微摩尔(500和1000微克)/动物,i.c.v.](PLA2抑制剂)对加压素诱导的血浆儿茶酚胺升高基本无效。这些结果表明,在大鼠中,加压素通过脑PLC和二酰基甘油脂肪酶依赖性机制引起肾上腺髓质去甲肾上腺素和肾上腺素的释放。