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Differential inhibition by cyclosporins of primary‐active ATP‐dependent transporters in the hepatocyte canalicular membrane
Author(s) -
Böhme Matthias,
Büchler Markus,
Müller Michael,
Keppler Dietrich
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80403-h
Subject(s) - cyclosporins , hepatocyte , chemistry , transporter , leukotriene c4 , antiporter , daunorubicin , biochemistry , vesicle , pharmacology , membrane , leukotriene , biology , in vitro , medicine , transplantation , genetics , asthma , leukemia , immunology , gene
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.