Induced Synthesis of Alkaline Phosphatase by Bile Acids in Rat Liver Cell Culture

Abstract

Synthesis of hepatic alkaline phosphatase is induced during cholestasis. To test whether bile acids, which accumulate to high levels in cholestasis, can stimulate hepatic alkaline phosphatase, we studied the ability of various bile acids and other detergents to stimulate hepatic alkaline phosphatase activity in primary monolayer cultures of adult rat hepatocytes. Alkaline phosphatase rose spontaneously in these cells during the first 2 days of culture and then stabilized. Taurocholate added to the medium on day 2 stimulated alkaline phosphatase in a dose-dependent fashion at concentrations from 10-2 to 1 MM (the highest concentration used). The rise in alkaline phosphatase required more than 6 hr to occur and could be blocked by cycloheximide. Other bile acids had similar effects; there was no correlation between the detergent properties of bile acids or their ability to disrupt biologic membranes and their propensity to induce hepatic alkaline phosphatase. 5'-Nucleotidase, an enzyme which increases in the plasma, but not in the hepatocyte during in vivo cholestasis, did not rise in cells incubated with taurocholate. We conclude that bile acids induce the synthesis of hepatic alkaline phosphatase in cultured rat hepatocytes, and speculate that such induction could account, at least in part, for the increase in hepatic levels of alkaline phosphatase observed in cholestasis.