Nguyen T T, De Léan A
Can J Physiol Pharmacol. 1987 May;65(5):823-7. doi: 10.1139/y87-132.
Cultured bovine chromaffin cells cosecrete catecholamines and enkephalins following cholinergic nicotinic stimulation. Initial reports on the inhibitory effect of clonidine on catecholamine secretion raised the possibility of a modulation of chromaffin cell function through a presynaptic adrenergic mechanism. The purpose of this work was to investigate the pharmacological characteristics of this inhibitory effect of clonidine on the cosecretion of catecholamines and enkephalins in 4-day-old cultured chromaffin cells. We observed that clonidine completely inhibits nicotine-stimulated secretion of both leucine-enkephalin and catecholamines with an IC50 of 34 microM. Treatment of chromaffin cells for 3 days with 100 nM reserpine leads to a 67% increase in nicotine-stimulated secretion of leucine-enkephalin without any effect on the IC50 of clonidine. In reserpine-treated chromaffin cells, norepinephrine (100 microM) inhibits only by 27% nicotine-stimulated secretion of leucine-enkephalin with an IC50 of 50 microM. Neither the alpha 2-adrenergic antagonist yohimbine nor the alpha 1-adrenergic antagonist prazosin could fully reverse the inhibitory effect of clonidine on leucine-enkephalin secretion at 10 nM. These results tend to rule out the role of alpha-adrenergic receptors in the mediation of clonidine inhibition of cosecretion in chromaffin cells.
经培养的牛嗜铬细胞在烟碱型胆碱能刺激后会共同分泌儿茶酚胺和脑啡肽。最初关于可乐定对儿茶酚胺分泌具有抑制作用的报道提出了通过突触前肾上腺素能机制调节嗜铬细胞功能的可能性。这项研究的目的是探究可乐定对4日龄培养的嗜铬细胞中儿茶酚胺和脑啡肽共同分泌的抑制作用的药理学特性。我们观察到可乐定能完全抑制尼古丁刺激的亮氨酸脑啡肽和儿茶酚胺的分泌，其半数抑制浓度（IC50）为34微摩尔。用100纳摩尔利血平处理嗜铬细胞3天，会使尼古丁刺激的亮氨酸脑啡肽分泌增加67%，而对可乐定的IC50没有任何影响。在经利血平处理的嗜铬细胞中，去甲肾上腺素（100微摩尔）仅能抑制27%的尼古丁刺激的亮氨酸脑啡肽分泌，其IC50为50微摩尔。10纳摩尔时，α2肾上腺素能拮抗剂育亨宾和α1肾上腺素能拮抗剂哌唑嗪均不能完全逆转可乐定对亮氨酸脑啡肽分泌的抑制作用。这些结果倾向于排除α肾上腺素能受体在介导可乐定抑制嗜铬细胞共同分泌中的作用。
