INHIBITORY EFFECT OF CYCLOSPORINE-A PEPTIDE ON RAT HEPATOCYTES PROLIFERATION INDUCED BY MITOGENS

Treatment of cultured rat hepatocytes with cyclosporin A (0.01-1 mu M) for 24, 48, or 72 h in the presence of insulin and epidermal growth f actor induced an inhibition on cell proliferation in a time-and concen tration-dependent manner, with an IC50 = 0.05 mu M CsA corresponding t o 48-h treatment. The inhibitory effect of CsA at less than or equal t o 0.1 mu M doses for 48 h on [H-3]thymidine uptake was reversed after withdrawal of the drug and subsequent addition of insulin plus EGF or serum; however, at 1 mu M CsA the effect was irreversible and numerous bright small vesicles were observed. The molecular mechanism involved in CsA action in hepatocytes seems to be independent on cAMP and pert ussis-toxin sensitive G proteins. (C) 1998 Elsevier Science Inc.