DIFFERENTIAL INHIBITION BY CYCLOSPORINS OF PRIMARY-ACTIVE ATP-DEPENDENT TRANSPORTERS IN THE HEPATOCYTE CANALICULAR MEMBRANE

The distinct ATP-dependent transporters for taurocholate, leukotriene C4, and daunorubicin, studied in rat liver canalicular membrane vesicl es, are sensitive to inhibition by cyclosporin A and its non-immunosup pressive analog PSC 833. K(i) values for cyclosporin A were 0.2, 3.4 a nd 1.5 muM for the transport of taurocholate, leukotriene C4, and daun orubicin, respectively. The corresponding K(i) values for PSC 833 were 0.6, 29, and 0.3 muM. Both inhibitors were competitive with respect t o the three substrates. The cyclosporins serve as new and potent tools to interfere with different potency with the distinct ATP-dependent e xport carriers in the hepatocyte canalicular membrane.