Hypercholeresis induced by norchenodeoxycholate in biliary fistula rodent.
The biliary recovery and effect on bile flow and biliary bicarbonate secretion of infused norchenodeoxycholate (nor-CDC), the synthetically prepared C23 homologue of chenodeoxycholate (CDC), were defined in the anesthetized biliary fistula hamster, rat, and guinea pig and compared with those of its taurine conjugate as well as those of the natural C24 bile acid, CDC. In the hamster and rat, nor-CDC was recovered slowly in bile in contrast to its taurine conjugate or CDC. Hepatic biotransformation of nor-CDC was complex. Little amidation with glycine or taurine occurred and the compound was recovered in bile in unchanged form, in the form of hydroxylated derivatives as well as glucuronates and sulfates, the proportion varying in the different species. In contrast, CDC was efficiently amidated with glycine or taurine. The taurine conjugate of nor-CDC was secreted largely unchanged. Nor-CDC infusion caused a striking hypercholeresis in the hamster (108 microliters bile/mumol bile acid in bile) and in the rat (220 microliters/mumol); these values for bile acid-dependent flow far exceed those reported for any other natural bile acid to date in these species. The induced hypercholeresis was of canalicular origin and was accompanied by an enrichment in bicarbonate ion concentration as well as increased bicarbonate output. The taurine conjugate of nor-CDC did not display hypercholeretic properties in the hamster. In the guinea pig, whose native bile is bicarbonate-rich relative to other species, nor-CDC was only mildly hypercholeretic relative to CDC and caused no change in bicarbonate concentration. Thus shortening the side chain of a natural dihydroxy bile acid by a single carbon atom formed a compound that underwent a different hepatic biotransformation than that of most natural bile acids and induced a bicarbonate-rich canalicular choleresis far greater than that which can be explained by current theories of bile formation.
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001646:Bile / Q000187:drug effects / Q000502:physiology; D001647:Bile Acids and Salts / Q000502:physiology*; D001658:Biliary Fistula; D001711:Biotransformation; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006224:Cricetinae; D004896:Erythritol / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D008647:Mesocricetus; D051381:Rats
C051380:23-norchenodeoxycholic acid; D001639:Bicarbonates; D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D004896:Erythritol