Effects of cardiovascular drugs on ATPase activity of P-glycoprotein in plasma membranes and in purified reconstituted form
Effects of cardiovascular drugs on ATPase activity of P-glycoprotein in plasma membranes and in purified reconstituted form
复制标题
DOI：
10.1016/s0005-2736(97)00185-5
复制
发表时间：
1998-02-02
影响因子：
3.4
通讯作者：
Senior, AE
中科院分区：
文献类型：
--
作者：
Rebbeor, JF;Senior, AE
采用ATP酶测定法定量评价药物与P-糖蛋白（Pgp）的相互作用。使用了两个实验系统，（i）从多药耐药细胞系分离的质膜，其含有30%的Pgp作为总膜蛋白的部分，和（ii）纯化的重组Pgp。心血管活性药物维拉帕米、奎尼丁、地尔硫卓、硝苯地平和一系列洋地黄类似物直接与Pgp相互作用，如对两个系统中ATP酶的影响所示。计算药物结合的表观亲和力。洋地黄毒苷和维拉帕米之间存在直接竞争。根据结果，预期在Pgp水平上存在体内药物相互作用。这种方法似乎非常适合于经验确定药物与Pgp的相互作用，并预测药物-药物相互作用。(C)1998年Elsevier Science B.V.
Drug interactions with P-glycoprotein (Pgp) were quantitatively assessed using ATPase assay. Two experimental systems were used, (i) plasma membranes isolated from a multidrug-resistant cell line, which contained 30% Pgp as fraction of total membrane protein, and (ii) purified reconstituted Pgp. The cardioactive drugs verapamil, quinidine, diltiazem, nifedipine, and a series of digitalis analogs, interacted directly with Pgp as shown by effects on ATPase in both systems. Apparent affinities of drug binding were calculated. Direct competition was shown between digitoxin and verapamil. Drug-drug interaction in vivo at the level of Pgp is expected from the results. This approach seems well-suited for empirical determination of drug interactions with Pgp, and prediction of drug-drug interactions. (C) 1998 Elsevier Science B.V.