Regulation of bile acid synthesis. I. Effects of conjugated ursodeoxycholate and cholate on bile acid synthesis in chronic bile fistula rat

Bile acid synthesis is thought to be regulated by a negative feedback mechanism which is presumably dependent upon the flux of bile acids in the enterohepatic circulation. To characterize further the role of bile acids in regulation of bile acid synthesis, we have administered pure taurine or glycine conjugates of ursodeoxycholic acid or cholic acid to chronic bile fistula rats by continuous intraduodenal infusion, thus simulating restoration of the enterohepatic circulation. The effects of these bile salt infusions on bile acid synthesis, biliary cholesterol and phospholipid secretion and on the activities of the hepatic microsomal enzymes cholesterol 7α‐hydroxylase and HMG‐CoA reductase were evaluated. Because the rate of biliary bile salt secretion in rats with intact exteriorized enterohepatic circulation averaged 27.1 ± 1.4 pinoles per 100 gm rat per hr, infusion rates for bile fistula studies were chosen to match (24 to 36 μmoles per 100 gm rat per hr) or exceed (48 μmoles per 100 gm rat per hr) this physiological flux.