Interaction of verapamil and other calcium channel blockers with alpha 1- and alpha 2-adrenergic receptors.
Interaction of verapamil and other calcium channel blockers with alpha 1- and alpha 2-adrenergic receptors.
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维拉帕米和其他钙通道阻滞剂与α1-和α2-肾上腺素能受体的相互作用。
DOI：
10.1161/01.res.52.2.226
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发表时间：
1983
影响因子：
20.1
通讯作者：
Insel,PA
中科院分区：
文献类型：
--
作者：
Motulsky,HJ;Snavely,MD;Hughes,RJ;Insel,PA
为了确定先前证明的维拉帕米与放射性配体结合α-肾上腺素能受体的竞争的特异性，我们研究了钙通道阻滞剂与几种组织上的α 1-和α 2-肾上腺素能受体的相互作用。维拉帕米竞争[3 H]哌唑嗪与α 1-肾上腺素能受体的结合，竞争[3 H]育亨宾与几种组织（人血小板、大鼠肾脏和心脏以及培养的肌肉细胞）中α 2-肾上腺素能受体的结合，解离常数为0.6-6 μ M。钙通道阻滞剂D 600、D591、芬地林和异戊烯胺（它们是维拉帕米的结构类似物）也竞争[3 H]育亨宾与人血小板的结合。另外两种钙通道阻滞剂，地尔硫卓和硝苯地平，不竞争[3 H]育亨宾结合人血小板或[3 H]哌唑嗪结合从大鼠心室制备的膜。我们使用[3 H]尼群地平结合，以确定假定的钙通道对大鼠心肌膜。硝苯地平和维拉帕米阻断了心室膜上的这些[3 H]尼群地平结合位点，但肾上腺素和哌唑嗪没有，表明心室α 1受体和钙通道是不同的。我们没有发现特异性[3 H]尼群地平结合人血小板。我们得出结论，维拉帕米与α-肾上腺素能受体的相互作用不是受体亚型或组织特异性的，与α-肾上腺素能受体的相互作用不是所有钙通道阻滞剂的特性，维拉帕米与α-肾上腺素能受体的相互作用及其与钙通道的相互作用发生在至少两个不同的位点。
To determine the specificity of the previously demonstrated competition of verapamil with radioligand binding to alpha-adrenergic receptors, we examined the interaction of calcium channel blockers with alpha 1- and alpha 2-adrenergic receptors on several tissues. Verapamil competed for [3H] prazosin binding to alpha 1-adrenergic receptors and for [3H]yohimbine binding to alpha 2-adrenergic receptors in several tissues (human platelets, rat kidney and heart, and cultured muscle cells) with dissociation constants of 0.6-6 microM. The calcium channel blockers D600, D591, fendiline, and prenylamine--which are structural analogues of verapamil--also competed for [3H]yohimbine binding to human platelets. Two other calcium channel blockers, diltiazem and nifedipine, did not compete for [3H] yohimbine binding to human platelets or [3H]prazosin binding to membranes prepared from rat ventricles. We used [3H]nitrendipine binding to identify putative calcium channels on rat myocardial membranes. Nifedipine and verapamil blocked these [3H]nitrendipine-binding sites on ventricular membranes, but epinephrine and prazosin did not, indicating that the ventricular alpha 1 receptors and calcium channels are distinct. We found no specific [3H]nitrendipine binding to human platelets. We conclude that the interaction of verapamil with alpha-adrenergic receptors is not receptor subtype or tissue specific, that interaction with alpha-adrenergic receptors is not a property of all calcium channel blockers, and that the interaction of verapamil with alpha-adrenergic receptors and its interaction with calcium channels occur at at least two distinct sites.