Verapamil competitively inhibits alpha 1-adrenergic and muscarinic but not beta-adrenergic receptors in rat myocardium.
Verapamil competitively inhibits alpha 1-adrenergic and muscarinic but not beta-adrenergic receptors in rat myocardium.
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维拉帕米竞争性抑制大鼠心肌中的α1-肾上腺素能受体和毒蕈碱受体，但不抑制β-肾上腺素能受体。
DOI：
10.1097/00005344-198205000-00025
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发表时间：
1982
影响因子：
3
通讯作者：
Insel,PA
中科院分区：
文献类型：
--
作者：
Karliner,JS;Motulsky,HJ;Dunlap,J;Brown,JH;Insel,PA
最近的研究表明，钙通道的拮抗作用可能不是维拉帕米等药物改变心肌功能的唯一机制。我们研究了维拉帕米对[~ 3 H]哌唑嗪（[α] 1-肾上腺素能）、[~ 3 H]奎宁环基二苯乙酸酯（QNB，毒蕈碱）和[~ 3 H]二氢烯丙洛尔（DHA，[β]-肾上腺素能）与大鼠心肌细胞膜结合的影响。维拉帕米以下列顺序竞争这些放射性配体的结合：[3 H]哌唑嗪>[3 H] QNB>[3 H] DHA（维拉帕米的K分别为0.6 [mu] M、7 [mu] M和72 [mu] M）。维拉帕米（10 [mu] M）竞争性抑制[3 H]哌唑嗪与大鼠心室膜的结合：[3 H]哌唑嗪的表观解离常数（KD）从0.13+/-0.02增加至1.5+/-0.6 nM（SD），而最大结合容量（Bmax）无变化。维拉帕米对[3 H]哌唑嗪亲和力的影响可通过冲洗膜完全逆转。维拉帕米衍生物D-600也抑制[3 H]哌唑嗪结合（KD= 1.1 [mu] M）。维拉帕米（30 [mu] M）竞争性抑制[3 H] QNB在心房和心室中的结合，并使[3 H] QNB的表观KD增加5倍（从0.07 nM增加到0.32 nM），而不降低Bmax。维拉帕米是一种不太有效的[3 H] DHA结合抑制剂，其作用是非竞争性的：100 [mu] M维拉帕米对DHA的KD没有改变，而Bmax降低了几倍。我们得出结论，维拉帕米，在临床上达到的浓度在心肌（~ 1 [mu] M），竞争性抑制结合[α] 1-肾上腺素能和毒蕈碱受体，这种抑制作用可能发挥作用的维拉帕米对心脏的影响。
Recent studies indicate that antagonism of calcium channels may not be the only mechanism whereby drugs such as verapamil alter myocardial function. We have examined the effect of verapamil on the binding of [3H] prazosin ([alpha] 1-adrenergic),[3H] quinuclidinyl benzilate (QNB, muscarinic) and [3H] dihydroalprenolol (DHA,[beta]-adrenergic) to membranes prepared from rat heart. Verapamil competed for the binding of these radioligands in the following rank order:[3H] prazosin>[3H] QNB>[3H] DHA (K, for verapamil= 0.6 [mu] M, 7 [mu] M, and 72 [mu] M, respectively). Verapamil (10 [mu] M) competitively inhibited [3H] prazosin binding to rat ventricular membranes: the apparent dissociation constant (KD) of [3H] prazosin increased from 0.13+/-0.02 to 1.5+/-0.6 nM (SD) without change in maximal binding capacity (Bmax). The effect of verapamil on the affinity of [3H] prazosin was completely reversed by washing the membranes. The verapamil derivative D-600 also inhibited [3H] prazosin binding (KD= 1.1 [mu] M). Verapamil (30 [mu] M) competitively inhibited [3H] QNB binding in both atria and ventricles and increased the apparent KD of [3H] QNB fivefold (from 0.07 nM to 0.32 nM) without decreasing Bmax. Verapamil was a less potent inhibitor of [3H] DHA binding and its effect was noncompetitive: the KD for DHA was unaltered by 100 [mu] M verapamil, while the Bmax decreased severalfold. We conclude that verapamil, at concentrations clinically achieved in the myocardium (~ 1 [mu] M), competitively inhibits binding to [alpha] 1-adrenergic and muscarinic receptors and that this inhibition may play a role in the effects of verapamil on the heart.