Hepatic and ileal transport and effect on biliary secretion of norursocholic acid and its conjugates in rats

The enterohepatic circulation of norursocholic acid (nUC) and its glycine (nUCG) and taurine (nUCT) conjugates was investigated in the rat; cholic acid (C) was studied as control. The biliary recovery of intravenously infused 14C-labeled bile acids was high: nUC, 88%; nUCG, 80%; nUCT, 99%, and C, 90%. Biliary recovery after the same bile acids were infused intraduodenally was similar: nUC, 90%; nUCG, 66%; nUCT, 97%; and C, 99%. The two conjugated bile acids, nUCG and nUCT, were not biotransformed during intestinal or hepatic transport; nUC was also secreted largely unchanged, but approximately 10% was secreted as an unknown conjugate or sulfate; C was completely conjugated with taurine or glycine. To compare the rates of active ileal transport, biliary recovery was measured after an in situ ileal perfusion technique. The rate of absorption of nUC, nUCG, and nUCT was one-fourth to one-half that of cholyltaurine, which served as control. Competition experiments indicated that the same transport system was involved. When infused intravenously, nUC, nUCG, and nUCT induced far less biliary lipid secretion than an identical dose of C; the secretion of both phospholipid and cholesterol was decreased, cholesterol to a greater extent than phospholipid. It is concluded that nUC and its conjugates are well transported by the ileum, are efficiently secreted into bile without undergoing appreciable hepatic biotransformation, and induce bile flow as other hydrophilic bile acids, but in contrast to C induce little phospholipid and cholesterol secretion into bile.