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  • Title: Inhibition of taurocholate transport by cyclosporin A in cultured rat hepatocytes.
    Author: Kukongviriyapan V, Stacey NH.
    Journal: J Pharmacol Exp Ther; 1988 Nov; 247(2):685-9. PubMed ID: 3183963.
    Abstract:
    Cyclosporin A, a powerful immunosuppressant, has been shown to interfere with the transport of bile salts and other substrates in isolated rat liver cells and to suppress bile flow and bile salt secretion in situ. Cyclosporin A was added to primary hepatocyte cultures just before taurocholate to study the immediate effects on transport. In prolonged exposure experiments cyclosporin A was dissolved in culture media. Efflux was studied by preloading cultured cells with [14C]taurocholate and then changing to sodium-free buffer containing no taurocholate. Cyclosporin A inhibited the uptake and efflux of taurocholate in a competitive manner when added just before determination of transport. Hepatocyte cultures which were pre-exposed to cyclosporin A (1-25 microM) for 18 hr and then washed, also showed a significantly lower taurocholate uptake. The longer the pre-exposure time the greater was the suppression. However, the inhibition could be reversed gradually by incubation of cultured cells in fresh media, complete reversal being attained within 3 hr. These results indicate that cyclosporin A competitively inhibits the taurocholate transport system. The interaction between cyclosporin A and transport components is rapid and long lasting but reversible.
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