Induction of hepatic alkaline phosphatase by colchicine: role of cholestasis and bile acids.
We studied the induction of hepatic alkaline phosphatase by colchicine, a drug which impairs bile flow. By analogy to bile duct obstruction, where retained bile acids induce alkaline phosphatase, we hypothesized that the mechanism of induction involves the drug's cholestatic property and subsequent intrahepatic retention of bile acids. After administering colchicine to bile-fistula rats, we monitored bile flow. In colchicine-treated rats which did not develop cholestasis, we varied the transhepatic flux of taurocholate 15-fold over the physiologic range in order to study the role of intrahepatic bile acids. Induction of alkaline phosphatase was observed when cholestasis was absent and the bile acid flux was 5% of normal. The magnitude of enzyme induction was not augmented by increasing the transhepatic flux of taurocholate. The results demonstrate that colchicine induces hepatic alkaline phosphatase by a mechanism which operates independently of cholestasis and is not modified by the level of bile acid in the liver.
D000469:Alkaline Phosphatase / Q000096:biosynthesis*; D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology*; D002779:Cholestasis / Q000139:chemically induced / Q000201:enzymology*; D003078:Colchicine / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D013656:Taurocholic Acid; D000469:Alkaline Phosphatase; D003078:Colchicine