AJP - Gastrointestinal and Liver Physiology, Vol 252, Issue 2 219-G228, Copyright © 1987 by American Physiological Society
Hypercholeresis induced by norchenodeoxycholate in biliary fistula rodent
K. R. Palmer, D. Gurantz, A. F. Hofmann, L. M. Clayton, L. R. Hagey and S. Cecchetti
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.
