Specific binding of [3H]nitrendipine to membranes from coronary arteries and heart in relation to pharmacological effects. Paradoxical stimulation by diltiazem.
Specific binding of [3H]nitrendipine to membranes from coronary arteries and heart in relation to pharmacological effects. Paradoxical stimulation by diltiazem.
复制标题
[3H]尼群地平与冠状动脉和心脏膜的特异性结合与药理作用的关系。
DOI：
10.1016/0006-291x(82)91838-1
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发表时间：
1982
影响因子：
3.1
通讯作者：
Schwartz,A
中科院分区：
文献类型：
--
作者：
DePover,A;Matlib,MA;Lee,SW;Dubé,GP;Grupp,IL;Grupp,G;Schwartz,A
在猪冠状动脉的微粒体（KD=1.6 nM; Bmax=35 fmol/mg）和犬心脏的纯化肌膜（KD=0.11 nM; Bmax=230 fmol/mg）中，已鉴定出钙通道抑制剂[3 H]尼群地平的高亲和力结合位点。[3 H]尼群地平与冠状动脉微粒体的结合被硝苯地平完全抑制，部分被维拉帕米和D 600抑制，令人惊讶的是，被d-顺式地尔硫卓刺激，但不被活性较低的异构体1-顺式地尔硫卓刺激。在1 nM尼群地平或100 nM d-顺式地尔硫卓时，KCl去极化冠状动脉环的半数最大舒张发生在缓慢过程中。在狗小梁条中，尼群地平引起负性肌力反应（ED 50 =1μM）。这些结果表明，可能有多个结合位点的不同的“亚类”的钙通道抑制剂，药物结合位点可能是不同的分子实体从推定的钙通道。
High affinity binding sites for the calcium channel inhibitor [3H]nitrendipine have been identified in microsomes from pig coronary arteries (KD=1.6 nM; Bmax=35 fmol/mg) and in purified sarcolemma from dog heart (KD=0.11 nM; Bmax=230 fmol/mg). [3H]nitrendipine binding to coronary artery microsomes was completely inhibited by nifedipine, partially by verapamil and D600 and, surprisingly, was stimulated by d-cis-diltiazem but not by 1-cis-diltiazem, a less active isomer. Half-maximal relaxation of KCl-depolarized coronary rings occurred in a slow process at 1 nM nitrendipine or 100 nM d-cis-diltiazem. In dog trabecular strips, nitrendipine caused a negative inotropic response (ED50=1μM). These results suggest that there may be multiple binding sites for different “subclasses” of calcium channel inhibitors, and that drug binding sites may be different molecular entities from the putative calcium channels.