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首页> 外文期刊>Cell biology international. >CJX1, an amlodipine derivative, interacts with ATPase of human P-glycoprotein.
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CJX1, an amlodipine derivative, interacts with ATPase of human P-glycoprotein.

机译：氨氯地平衍生物CJX1与人P-糖蛋白的ATPase相互作用。

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摘要

Our aim has been to elucidate the possible mechanism of CJX1, an amlodipine derivative, in the modulation of P-gp function by determining its effect on P-gp ATPase activity. Basal P-gp ATPase activity was increased by CJX1 with half-maximal activity concentration (Km) of 8.6+/-1.4 microM. Kinetic analysis indicated a non-competitive inhibition of Verapamil (Ver)-stimulated P-gp ATPase activity by CJX1 and competitive inhibition of CJX1-stimulated P-gp ATPase activity by tetrandrine (Tet). The effect of CsA on CJX1-stimulated and Ver-stimulated P-gp ATPase activity was non-competitive and competitive inhibition, respectively. These findings implying that CJX1 and Tet can bind P-gp either on overlapping sites or distinct but interacting sites, while CJX1 and Ver as well as CsA can bind P-gp on separated sites in K562/DOX cells. Furthermore, the combined effect of CJX1 and Ver has been evaluated isobolographically in numerous fixed-ratio combinations of 1:1, 1:2, 1:4, 1:8, 1:10 in K562/DOX cells. The results show that mixtures of both drugs at these fixed-ratios exerted synergistic interactions, indicating that when the two reverses that bind P-gp on separated sites are combined, each can contribute to the overall interaction with P-gp, leading to the greater effect than that by either agent alone.
机译：我们的目标是通过确定CJX1（一种氨氯地平衍生物）对P-gp ATPase活性的影响来阐明其对P-gp功能的调节的可能机制。 CJX1增加了基础P-gp ATPase活性，最大活性浓度（Km）的一半为8.6 +/- 1.4 microM。动力学分析表明，CJX1对Verapamil（Ver）刺激的P-gp ATPase活性具有非竞争性抑制作用，粉防己碱（Tet）对CJX1刺激的P-gp ATPase活性具有竞争性抑制作用。 CsA对CJX1刺激和Ver刺激的P-gp ATPase活性的影响分别是非竞争性和竞争性抑制。这些发现暗示CJX1和Tet可以在重叠位点或不同但相互作用的位点上结合P-gp，而CJX1和Ver以及CsA可以在K562 / DOX细胞的分离位点上结合P-gp。此外，已在K562 / DOX细胞中以1：1、1：2、1：4、1：8、1：10的众多固定比例组合进行等效线描记法评估了CJX1和Ver的联合作用。结果表明，两种药物在这些固定比例下的混合物产生协同相互作用，表明当结合在单独位点结合P-gp的两种反向结合时，每种均可促进与P-gp的整体相互作用，从而导致更大的相互作用。效果比任何一种单独使用的效果都要好。

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