Cyclosporin A protects liver cells against phalloidin: Potent inhibition of the inward transport of cholate and phallotoxins

Cyclosporin A at concentrations of more than 10 nM protects isolated hepatocytes against the action of phalloidin. Cyclosporin A at 100 nM inhibits the uptake of demethyl³H]phalloin by 50%, and at 5 μM also that of ¹⁴C]cholate. This inhibition is independent of the preincubation period and is not reversed by washing the cells. With a 30–60-fold excess of cyclosporin A, affinity labeling of plasma membrane proteins using 12 μM ³H]isothiocyanatobenzamido cholate was reduced to 40–60% of the control. These findings indicate that transport inhibition by cyclosporin A in liver cells cannot be explained by simple competition on the level of the membrane protein(s) involved.