MECHANISMS OF HEPATIC TRANSPORT OF CYCLOSPORIN A : AN EXPLANATION FOR ITS CHOLESTATIC ACTION ?

The hepatic transport of the immunosuppressive Cyclosporin A (CyA) was studied using liposomal phospholipid membranes, freshly isolated rat hepatocytes and bile canalicular plasma membrane vesicles from rat liver. The Na+dependent, saturable uptake of the bile acid 3H-taurocholate into isolated rat liver cells was apparently competitively inhibited by CyA. However, the uptake ofCyA into the cells was neither saturable, nor temperature-dependent nor Na+dependent, nor could it be inhibited by bile salts or CyA-derivatives, indicating passive diffusion.