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.