Competitive inhibition of the uptake of demethylphalloin by cholic acid in isolated hepatocytes. Evidence for a transport competition rather than a binding competition.

Cholic acid inhibits the uptake of demethylphalloin (DMP), in a competitive manner. The bile acid increases the Michaelis constant but not Vmax of the inward transport. The inhibition constant Ki for cholate was found to be 8 microM. Cholate competes for the transport system but not for intracellular binding of phallotoxins. Various experimental data presented in this paper exclude an accumulation of phallotoxins in hepatocytes by intracellular binding only. Preincubation of hepatocytes with small concentration of either (3H)-demethylphalloin or (14C)-cholate and subsequent treatment with high concentrations of the non-labelled compounds reduces the intracellular concentration of both radioactive substrates. In accordance with earlier findings the above results suggest a common component needed for the transport of both phallotoxins and cholic acid.