Inhibition of mechanosensitivity in visceral primary afferents by GABAB receptors involves calcium and potassium channels
Inhibition of mechanosensitivity in visceral primary afferents by GABAB receptors involves calcium and potassium channels
复制标题
DOI：
10.1016/j.neuroscience.2005.09.016
复制
发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Blackshaw, LA
中科院分区：
文献类型：
--
作者：
Page, AJ;O'Donnell, TA;Blackshaw, LA
GABA（B）受体抑制内脏传入的机械敏感性。这与导致胃食管反流的事件触发减少相关，具有重要的治疗效果。在其他神经元系统中，GABA（B）受体激活可能通过G蛋白与N型Ca 2+通道开放减少、内向整流性K+通道开放增加以及对许多细胞内信使的影响有关。本研究旨在探讨GABA（B）受体激动剂巴氯芬对迷走神经传入机械感受器功能的抑制作用中Ca ~（2+）和K ~+通道的作用。在离体条件下研究了雪貂胃食管迷走神经三种类型（粘膜、张力和张力粘膜感受器）对分级机械刺激的反应。定量单独巴氯芬（200 μ M）对这些反应的影响，以及巴氯芬在G-蛋白偶联内向整流钾通道阻断剂Rb+（4.7 mM）和/或N-型钙通道阻断剂ω-芋螺毒素GVIA（0.1 μ M）存在下的影响。巴氯芬抑制粘膜受体mechanosensitivity被取消这两种阻滞剂。其对张力粘膜受体的抑制作用被两者部分减弱。巴氯芬对张力感受器的抑制作用不受影响。这些数据表明，GABA（B）受体的抑制作用是通过粘膜、张力和张力粘膜受体中的不同途径介导的，其机制涉及N型Ca 2+通道和内向整流K+通道等。(c)2005由Elsevier Ltd代表IBRO出版。
GABA(B) receptors inhibit mechanosensitivity of visceral afferents. This is associated with reduced triggering of events that lead to gastro-esophageal reflux, with important therapeutic consequences. In other neuronal systems, GABA(B) receptor activation may be linked via G-proteins to reduced N-type Ca2+ channel opening, increased inward rectifier K+ channel opening, plus effects on a number of intracellular messengers. Here we aimed to determine the role of Ca2+ and K+ channels in the inhibition of vagal afferent mechanoreceptor function by the GABA(B) receptor agonist baclofen. The responses of three types of ferret gastro-esophageal vagal afferents (mucosal, tension and tension mucosal receptors) to graded mechanical stimuli were investigated in vitro. The effects of baclofen (200 mu M) alone on these responses were quantified, and the effects of baclofen in the presence of the G-protein-coupled inward rectifier potassium channel blocker Rb+ (4.7 mM) and/or the N-type calcium channel blocker omega-conotoxin GVIA (0.1 mu M). Baclofen inhibition of mucosal receptor mechanosensitivity was abolished by both blockers. Its inhibitory effect on tension mucosal receptors was partly reduced by both. The inhibitory effect of baclofen on tension receptors was unaffected. The data indicate that the inhibitory action of GABA(B) receptors is mediated via different pathways in mucosal, tension and tension mucosal receptors via mechanisms involving both N-type Ca2+ channels and inwardly rectifying K+ channels and others. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.