Biliary Excretion and Enterohepatic Circulation of [14C]5-Hydroxytryptamine in Normal and Cirrhotic Rats

Abstract

Carbon-14-labeled 5-hydroxytryptamine (5HT) was administered intraportally to normal and cirrhotic rats, and urine and bile were collected periodically for periods up to 6, and occasionally up to 10 hr. 14C-labeled 5HT metabolites were separated with the use of two-dimensional paper chromatography, and the radioactivity of nine metabolites of 5HT was measured. Cirrhotic rats excreted 14C metabolites into urine in less quantity than did normal rats. In addition, the biliary excretion of 14C-labeled 5HT metabolites was markedly depressed in cirrhotic rats. The preferential occurrence of glucuronide conjugates was demonstrated in both the urine and bile of cirrhotic animals. 14C-labeled 5-hydroxytryptophol conjugates decreased and relabeled 5HT conjugates increased in cirrhotic rats. In normal animals, at least one-third of the 14C-labeled 5HT metabolites excreted into the bile go through the enterohepatic circulation, and a significant proportion of these can be found again in bile after intrajejunal administration of prelabeled bile.