Inhibition by cyclosporin A of Adenosine triphosphate-dependent transport from the hepatocyte into bile

• Verfasst von: Kadmon, Martina [VerfasserIn]
• Verfasst von: Klünemann, Cornelia [VerfasserIn]
• Verfasst von: Böhme, Matthias [VerfasserIn]
• Verfasst von: Ishikawa, Toshihisa [VerfasserIn]
• Verfasst von: Gorgas, Karin [VerfasserIn]
• Verfasst von: Otto, Gerd [VerfasserIn]
• Verfasst von: Herfarth, Christian [VerfasserIn]
• Verfasst von: Keppler, Dietrich [VerfasserIn]
• Titel: Inhibition by cyclosporin A of Adenosine triphosphate-dependent transport from the hepatocyte into bile
• Verf.angabe: Martina Kadmon, Cornelia Klünemann, Matthias Böhme, Toshihisa Ishikawa, Karin Gorgas, Gerd Otto, Christian Herfarth, Dietrich Keppler
• E-Jahr: 1993
• Jahr: May 1993
• Umfang: 8 S.
• Fussnoten: Elektronische Reproduktion der Druck-Ausgabe 10. Juni 2016 ; Gesehen am 24.04.2025
• Titel Quelle: Enthalten in: Gastroenterology
• Ort Quelle: New York, NY : Elsevier, 1949
• Jahr Quelle: 1993
• Band/Heft Quelle: 104(1993), 5, Seite 1507-1514
• ISSN Quelle: 1528-0012
• DOI: doi:10.1016/0016-5085(93)90363-H
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1923555480

Abstract

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.