Differential inhibition by cyclosporins of primary‐active ATP‐dependent transporters in the hepatocyte canalicular membrane

[摘要]

The distinct ATP-dependent transporters for taurocholate, leukotriene C4, and daunorubicin, studied in rat liver canalicular membrane vesicles, are sensitive to inhibition by cyclosporin A and its non-immunosuppressive analog PSC 833. K _i values for cyclosporin A were 0.2, 3.4 and 1.5 μM for the transport of taurocholate, leukotriene C4, and daunorubicin, respectively. The corresponding K _i values for PSC 833 were 0.6, 29, and 0.3 μM. Both inhibitors were competitive with respect to the three substrates. The cyclosporins serve as new and potent tools to interfere with different potency with the distinct ATP-dependent export carriers in the hepatocyte canalicular membrane.

[学科分类] 生物化学/生物物理

[关键词] ATP-dependent transport;Daunorubicin;LTC4;Multidrug resistance;P-glycoprotein;Taurocholate;BSEC;bile salt export carrier;CsA;cyclosporin A;IC50;concentration required for 50% inhibition;LTEC;leukotriene export carrier;MDEC;multidrug export carrier;MDR;multidrug resistance;SDZ PSC 833 or PSC 833;(3'-oxo-4-butenyl-4-methyl-threoninel)-(Val2)-cyclosporin;TC;taurocholate;LTC4;leukotriene C4