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 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 tra...

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Veröffentlicht in:	FEBS letters 1993-10, Vol.333 (1), p.193-196
Hauptverfasser:	Böhme, Matthias, Büchler, Markus, Müller, Michael, Keppler, Dietrich
Format:	Artikel
Sprache:	eng
Schlagworte:	Adenosine Triphosphate - physiology Animals ATP-dependent transport Bile Canaliculi - metabolism Biological and medical sciences Biological Transport, Active - drug effects BSEC, bile salt export carrier Carrier Proteins - antagonists & inhibitors Carrier Proteins - metabolism Cell Membrane - metabolism Cell physiology CsA, cyclosporin A Cyclosporins - pharmacology Daunorubicin Daunorubicin - metabolism Fundamental and applied biological sciences. Psychology IC50, concentration required for 50% inhibition In Vitro Techniques Leukotriene C4 - metabolism LTC4 LTC4, leukotriene C4 LTEC, leukotriene export carrier Male MDEC, multidrug export carrier MDR, multidrug resistance Membrane and intracellular transports Molecular and cellular biology Multidrug resistance P-glycoprotein Rats Rats, Wistar SDZ PSC 833 or PSC 833, (3'-oxo-4-butenyl-4-methyl-threoninel)-(Val2)-cyclosporin Taurocholate Taurocholic Acid - metabolism TC, taurocholate
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Zusammenfassung:	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.
ISSN:	0014-5793 1873-3468
DOI:	10.1016/0014-5793(93)80403-H