Inhibition by cyclosporin A of Adenosine triphosphate-dependent transport from the hepatocyte into bile
Background: Immunosuppressive treatment with cyclosporin A may be associated with impaired hepatobiliary elimination of bile salts and with cholestasis. Inhibition by cyclosporin A of the primary-active adenosine triphosphate (ATP)-dependent transport systems responsible for excretion of bile salts...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
May 1993
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| In: |
Gastroenterology
Year: 1993, Jahrgang: 104, Heft: 5, Pages: 1507-1514 |
| ISSN: | 1528-0012 |
| DOI: | 10.1016/0016-5085(93)90363-H |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/0016-5085(93)90363-H Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/001650859390363H 
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| Verfasserangaben: | Martina Kadmon, Cornelia Klünemann, Matthias Böhme, Toshihisa Ishikawa, Karin Gorgas, Gerd Otto, Christian Herfarth, Dietrich Keppler |
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| 245 | 1 | 0 | |a Inhibition by cyclosporin A of Adenosine triphosphate-dependent transport from the hepatocyte into bile |c Martina Kadmon, Cornelia Klünemann, Matthias Böhme, Toshihisa Ishikawa, Karin Gorgas, Gerd Otto, Christian Herfarth, Dietrich Keppler |
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| 520 | |a Background: Immunosuppressive treatment with cyclosporin A may be associated with impaired hepatobiliary elimination of bile salts and with cholestasis. Inhibition by cyclosporin A of the primary-active adenosine triphosphate (ATP)-dependent transport systems responsible for excretion of bile salts and cysteinyl leukotrienes across the hepatocyte canalicular membrane into bile may explain the cholestatic side effect. Methods: ATP-dependent transport of bile salt and of cysteinyl leukotrienes was studied in human liver plasma membrane vesicles and additionally in rat liver plasma membrane vesicles enriched in canalicular membranes. Results: Inhibition of ATP-dependent taurocholate transport in human liver by 50% was measured at 3 μmol/L cyclosporin A and at 4 μmol/L fujimycin. Kinetic analyses in rat liver indicated non-competitive inhibition by cyclosporin A with respect to ATP and competitive inhibition with respect to taurocholate with inhibition constant (Ki) values of 1.0 and 0.3 μmol/L, respectively. Conclusions: The ATP-dependent export carriers for bile salts and cysteinyl leukotrienes in the hepatocyte canalicular membrane are novel targets for inhibitory side effects of cyclosporin A. Inhibition of ATP-dependent bile salt transport may induce cholestasis. | ||
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