Effects of CJX1,an amlodipine derivative,on ATPase activity of human P-glycoprotein in resistant tumor cells
- VernacularTitle:氨氯地平衍生物CJX1对人耐药肿瘤细胞P-gp ATP酶活性的影响
- Author:
Biansheng JI
;
Ling HE
- Publication Type:Journal Article
- Keywords:
P-glycoprotein;
CJX1;
ATPase
- From:
Chinese Pharmacological Bulletin
2003;0(12):-
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate interaction of CJX1,an amlodipine derivative,with ATPase activity of human P-glycoprotein.Methods Plasma membranes were prepared from K562/DOX cells,the P-gp adenosine triphosphatase activity of K562/DOX cell membranes was estimated by measuring inorganic phosphate liberation.Results The basal P-gp ATPase activity was increased by CJX1 with half-maximal activity concentration (Km) of (8.6?1.4) ?mol?L-1,CJX1 might interact with P-gp with a higher affinity and exhibit more potent effect than Verapamil (Ver).Kinetic analysis indicated a non-competitive inhibition of Ver-stimulated P-gp ATPase activity by CJX1 and a competitive inhibition of CJX1-stimulated P-gp ATPase activity by tetrandrine (Tet),moreover,the effect of CsA on CJX1-stimulated and Ver-stimulated P-gp ATPase activity showed a non-competitive and a competitive inhibition respectively.Conclusion CJX1 and Tet can bind P-gp on overlapping sites,while CJX1 and Ver as well as CsA can bind P-gp on separated sites in K562/DOX cells.
