Influence of tauroursodeoxycholic and taurodeoxycholic acids on hepatic metabolism and biliary secretion of phosphatidylcholine in the isolated rat liver.
Studies were carried out using an isolated rat liver system to define: the contribution of exogenous phosphatidylcholine (PC) to biliary phospholipid secretion; and its hepatic metabolism during perfusion of the livers with conjugated bile salts with different hydrophilic/hydrophobic properties. A tracer dose of sn-1-palmitoyl-sn-2-[14C]linoleoylPC was injected as a bolus into the recirculating liver perfusate, under constant infusion of 0.75 mumol/min of tauroursodeoxycholate or taurodeoxycholate. The effects on bile flow, biliary lipid secretion, 14C disappearance from the perfusate and its appearance in bile, as well as hepatic and biliary biotransformation were determined. With both the bile salts, about 40% of the [14C]PC was taken up by the liver from the perfusate over 100 min. During the same period less than 2% of the given radioactivity was secreted into bile. More than 95% of the 14C recovered in bile was located within the identical injected PC molecular species. The biliary secretion of labeled as well as unlabeled PC, however, was significantly higher in livers perfused with taurodeoxycholate than tauroursodeoxycholate, while the reverse was observed with respect to bile flow and total bile salt secretion. The exogenous PC underwent extensive hepatic metabolization which appeared to be influenced by the type of bile salt perfusing the liver. After 2 h perfusion, the liver radioactivity was found, in decreasing order, in PC, triacylglycerol, phosphatidylethanolamine and diacylglycerol. In addition, the specific activity of triacylglycerol was significantly higher in tauroursodeoxycholate than in taurodeoxycholate-perfused livers (P less than 0.025), while the reverse was true for the specific activity of hepatic PC (P less than 0.01). Because taurodeoxycholate and tauroursodeoxycholate showed opposite effects on both biliary lipid secretion and hepatic PC biotransformations, we conclude that the hepatic metabolism of glycerolipids is influenced by the physiochemical properties of bile salts.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives*; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D013657:Taurodeoxycholic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D002250:Carbon Radioisotopes; D010713:Phosphatidylcholines; D014280:Triglycerides; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; C031655:ursodoxicoltaurine