The influence of conjugation of cholic acid on its uptake and secretion: hepatic extraction of taurocholate and cholate in the dog

Abstract

1. Sodium taurocholate or cholate was administered systemically at a constant rate of about 2.9 mumole/min.kg body wt. to anaesthetized dogs in which the common bile duct had been cannulated. In steady-state conditions blood was sampled from systemic and hepatic veins and the fraction of bile salt removed in a single passage through the liver was determined. Total hepatic blood flow was estimated by application of the Fick principle.2. The hepatic extraction fraction for synthetic taurocholate in ten experiments was 92%+/-5% (S.D.) over the blood flow range encountered (1.1-2.8 ml./min.g liver). The extraction of cholate extensively conjugated in the liver before excretion into bile was 79%+/-8% (S.D.) (twenty-one observations, thirteen experiments). In circumstances of similar hepatic blood flow the extraction of cholate transferred to bile in the free form (after acute taurine depletion) was significantly less than that of either synthetic taurocholate or cholate which could be actively conjugated before excretion. These results, which are discussed and criticized, support previous work on the advantage of conjugation in the transfer of cholic acid from blood to bile.3. The hepatic clearance of bile salt decreases with increasing administration rate, but the values obtained may be influenced by changes in hepatic blood flow. With regard to taurocholate an increase in total hepatic flow was observed when its administration rate exceeded about 5 mumole/min.kg body wt.4. The secretory maximum for glycocholate, a bile salt not normally found in dog bile, was of the same order as that for taurocholate.