Institute of Pharmacology, School of Medicine, Catholic University of the Sacred Heart, L.go F. Vito, Rome, Italy.
Eur J Pharmacol. 2010 Feb 25;628(1-3):207-13. doi: 10.1016/j.ejphar.2009.11.044. Epub 2009 Nov 27.
Ca(2+) inflow responsible for neurotransmitter release at most peripheral junctions is mainly mediated by activation of Ca(V)2.2 and Ca(V)2.1 channels. The aim of the present study was to characterize the voltage-gated Ca(2+) channels (VGCCs) responsible for the non-adrenergic non-cholinergic (NANC) relaxation and vasoactive intestinal polypeptide (VIP)-like immunoreactivity release in the rat gastric fundus. Precontracted longitudinal muscle strips of the rat gastric fundus were subjected to electrical field stimulation (EFS) under NANC conditions to evoke the relaxation and VIP-like immunoreactivity release. Nifedipine (1microM) completely relaxed the preparations, so that its effects on EFS-induced NANC relaxations could not be investigated. omega-Conotoxin GVIA (0.3-100nM) concentration-dependently reduced the amplitude of low frequency and the area under the curve (AUC) of high-frequency EFS-evoked relaxations (maximal reductions: approximately 55% and 42% of controls, respectively). The omega-conotoxin GVIA-resistant component of relaxation was not affected by omega-agatoxin IVA (300nM), omega-conotoxin MVIIC (100nM), SNX-482 (100nM) or flunarizine (1microM). omega-Conotoxin GVIA (30nM), omega-agatoxin IVA (30nM) and omega-conotoxin MVIIC (100nM) reduced high-frequency EFS-evoked VIP-like immunoreactivity release by approximately 70%, 27% and 35% of controls, respectively. omega-Conotoxin GVIA (30nM) plus omega-conotoxin MVIIC (100nM) almost abolished the EFS-induced VIP-like immunoreactivity outflow. In the rat gastric fundus, the activation of Ca(V)2.2 and P-type of Ca(V)2.1 channels is responsible for the EFS-induced VIP-like immunoreactivity release. In contrast, Ca(V)1 channels, novel VGCCs and/or molecular variants of VGCCs cloned to date may mediate a substantial component of the NANC relaxation.
在大多数外周连接处负责神经递质释放的 Ca(2+)内流主要是通过激活 Ca(V)2.2 和 Ca(V)2.1 通道来介导的。本研究的目的是描述负责大鼠胃底非肾上腺素能非胆碱能（NANC）松弛和血管活性肠肽（VIP）样免疫反应释放的电压门控 Ca(2+)通道（VGCCs）。在 NANC 条件下，用电刺激（EFS）使大鼠胃底的纵向肌条预先收缩，以引起松弛和 VIP 样免疫反应释放。硝苯地平（1μM）完全松弛了制剂，因此不能研究其对 EFS 诱导的 NANC 松弛的影响。ω-芋螺毒素 GVIA（0.3-100nM）浓度依赖性地降低低频和高频 EFS 诱导的松弛的幅度和曲线下面积（AUC）（最大减少：分别约为对照的 55%和 42%）。ω-芋螺毒素 GVIA 不敏感的松弛成分不受 ω-阿加毒素 IVA（300nM）、ω-芋螺毒素 MVIIC（100nM）、SNX-482（100nM）或氟桂利嗪（1μM）的影响。ω-芋螺毒素 GVIA（30nM）、ω-阿加毒素 IVA（30nM）和 ω-芋螺毒素 MVIIC（100nM）分别使高频 EFS 诱导的 VIP 样免疫反应释放减少约对照的 70%、27%和 35%。ω-芋螺毒素 GVIA（30nM）加 ω-芋螺毒素 MVIIC（100nM）几乎完全消除了 EFS 诱导的 VIP 样免疫反应流出。在大鼠胃底，Ca(V)2.2 和 P 型 Ca(V)2.1 通道的激活负责 EFS 诱导的 VIP 样免疫反应释放。相比之下，Ca(V)1 通道、新型 VGCCs 和/或迄今为止克隆的 VGCCs 的分子变体可能介导了相当一部分 NANC 松弛。
