Alkaline phosphatase activity in hepatic tissue and serum correlates with amount and type of bile acid load

Bile acids stimulate synthesis of alkaline phosphatase (ALPase) in the liver. We studied how alterations in bile acid type and load affect ATPase activity in hepatic tissue and in the serum. We increased the load of natural bile acids in rats by bile duct obstruction (BDO) or by creating a shunt between the common bile duct and superior vena cava (choledocho-caval shunt or CCS). Concentration of bile acids and ALPase activity in hepatic tissue rose more rapidly in the BDO model than in CCS. ALPase activity on the hepatocellular surface, normally confined to the canaliculus, spread outward to involve basolateral membrane in livers with high total hepatic ALPase activity. When the bile acid pool was reduced by a 12-hour biliary drainage in the CCS model, surface distribution of ALPase reverted to a nearly normal pattern. We substituted the endogenous bile acid pool with an equimolar amount of the single bile acid, taurocholic (TCA), tauroursocholic, taurohyocholic, or tauroursodeoxycholic acid in the CCS. The first two bile acids have a 12 alpha-hydroxyl group, whereas the latter two do not. After 12 hours, hepatic ALPase activity was increased with TCA or tauroursocholic substitution, but not with taurohyocholic or tauroursodeoxycholic. Again, surface distribution of ALPase activity correlated with the tissue ALPase activity. However, the serum activity increased significantly only with TCA, the most detergent of the bile acids. In bile fistula rats only infusion of TCA accelerated biliary secretion of ALPase. The above results suggest that hepatic synthesis and serum activity of ALPase are influenced by two different features of bile acids: the former by structure (the 12 alpha-hydroxyl group) and the latter by a physical property (detergency).