AJP - Gastrointestinal and Liver Physiology, Vol 241, Issue 4 337-G343, Copyright © 1981 by American Physiological Society
Nature of bile acid maximum secretory rate in the rat
W. G. Hardison, D. E. Hatoff, K. Miyai and R. G. Weiner
We studied the determinants of maximum bile acid secretory rate (SRm) in
the rat. The choledochocaval fistula rat model manifested a bile acid
secretory rate far in excess of the SRm previously reported for
taurocholate in this species. We studied the ability of various bile acid
solutions to maintain the high secretion rate in this model. Whole-rat
bile, but not taurocholate in 2% albumin nor rat bile with bile acid
content over 90% taurocholate, maintained secretion rate. We concluded that
the mixture of bile acids in rat bile was the most important determinant of
the high secretion rate and that the high rate was not due to a peculiarity
of the model itself nor to the infusion of biliary lipids together with
bile acids. Conventional determination of the SRm in the bile fistula rat
confirmed this impression, with the least toxic bile acids manifesting the
highest SRm. During infusion of taurocholate beyond the SRm, bile flow and
bile acid secretion rate fell. This was accompanied only by scattered focal
necrosis of single liver cells or of small aggregates of cells and not by
any diffuse subcellular morphological change. We believe the maximum bile
acid secretory rate is determined by toxicity of a specific bile acid for
the secretory mechanism rather than by a limitation in transport receptor
number as is usual with substances manifesting classical transport maxima.
The high SRm of the 7 beta-hydroxy bile acid, ursodeoxycholic acid, is
probably related to its very low toxicity. The high SRm in the
choledochocaval fistula rat is probably related to the presence of 7
beta-hydroxy muricholic acids in the bile of this species.
