Allosteric Modulation of [3H]Nitrendipine Binding to Cardiac and Cerebral Cortex Membranes by Amiodarone
Allosteric Modulation of [3H]Nitrendipine Binding to Cardiac and Cerebral Cortex Membranes by Amiodarone
复制标题
胺碘酮对[3H]尼群地平与心脏和大脑皮层膜结合的变构调节
DOI：
10.1097/00005344-198609000-00025
复制
发表时间：
1986
影响因子：
3
通讯作者：
P. Chatelain
中科院分区：
文献类型：
--
作者：
P. Nokin;M. Clinet;S. Swillens;C. Delisée;L. Meysmans;P. Chatelain
总结：用[~ 3 H]尼群地平作放射性配体，在豚鼠大脑皮层和大鼠心肌膜上进行竞争结合实验，研究抗心绞痛和抗心律失常药物胺碘酮与慢钙通道之间可能的相互作用。胺碘酮以明显竞争的方式从大脑皮层和心肌膜中取代特异性结合的[3 H]尼群地平。在饱和结合实验中，随着胺碘酮浓度的增加，[3 H]尼群地平的表观亲和力逐渐降低，而最大结合容量（Bmax）保持不变。地尔硫卓和维拉帕米都能逆转胺碘酮对[3 H]尼群地平与大脑皮层膜结合的抑制作用。总之，这些结果表明，胺碘酮通过作用于与钙通道相关的1，4-二氢吡啶结合位点发生变构相互作用的位点，对[3 H]尼群地平结合产生假竞争性抑制。这些数据与地尔硫卓、维拉帕米和胺碘酮存在共同结合位点相一致。这些观察结果进行了讨论与药物的药理学特性。
Summary: The possible interaction between the antianginal and antiarrhythmic drug amiodarone and the slow calcium channel was investigated by competition binding experiments in guinea-pig cerebral cortex and rat heart membranes using [3H]nitrendipine as radioligand. Amiodarone displaced specifically bound [3H]nitrendipine from cerebral cortex and cardiac membranes in an apparently competitive manner. In saturation binding experiments, apparent affinity for [3H]nitrendipine progressively decreased with increasing concentrations of amiodarone, whereas maximal binding capacity (Bmax remained unchanged. Both diltiazem and verapamil reversed the inhibitory effect of amiodarone on [3H]nitrendipine binding to cerebral cortex membranes. Together these results suggest that amiodarone exerts a pseudocompetitive inhibition on [3H]nitrendipine binding by acting at a site in allosteric interaction with the 1,4 dihydropyridine binding site associated with the calcium channel. The data are compatible with the existence of a common binding site for diltiazem, verapamil, and amiodarone. These observations are discussed in connection with the pharmacological properties of the drug.