The dual effect of glycocholate on hepatic dihydroxy bile acid excretion

Abstract

The effects of glycocholate infusion on biliary dihydroxy bile acid excretion were studied. Glycocholate initially enhanced, then, at infusion rates close to its maximum excretory capacity, inhibited dihydroxy bile acid output into bile. Since plasma levels of the latter were unchanged, these effects resulted from changes at the hepatocytic storage and transport sites. In experiments using theophylline, a bile salt-independent choleretic, there was no enhancement of dihydroxy bile acid output, indicating that factors other than the increased bile flow by the choleretic action of glycocholate must be considered. In experiments using dehydrocholate, a non-micelle-forming bile acid, enhancement of dihydroxy bile acid excretion was again observed, and hence, this phenomenon occurs regardless of micellar association. These observations, as well as the finding of considerable hepatic storage of the infused dihydroxy bile acids, suggested that their enhancement of excretion is brought about by the influx of a relatively large amount of glycocholate displacing them from hepatocytic storage sites into bile. The subsequent phase of inhibition of dihydroxy bile acid output into bile by infusion of glycocholate at levels close to its maximum excretory capacity suggested competitive inhibition for excretion since there were no changes in plasma levels of the former. This would indicate that a common transport process is shared by the major bile acids studied. Furthermore, since there were differences between deoxycholate and chenodeoxycholate in their enhancement and inhibition of output by glycocholate infusion, this would suggest that the bile acids share a common storage binding protein and transport carrier with different affinities for different bile acids.