AJP - Gastrointestinal and Liver Physiology, Vol 254, Issue 5 644-G649, Copyright © 1988 by American Physiological Society
Cholestasis and the interactions of sulfated glyco- and taurolithocholate with calcium
R. van der Meer, R. J. Vonk and F. Kuipers
Department of Nutrition, Netherlands Institute for Dairy Research, Ede.
To elucidate possible mechanisms of the differential cholestatic effect of
sulfated glyco- and taurolithocholate (SGLC and STLC) the interactions of
these bile acids with calcium were studied both in vitro and in vivo. In
vitro, SGLC was readily precipitated by Ca in physiological concentrations
(less than 5 mM). It appeared that only micelles of SGLC were precipitated
and that both the sulfate and the carboxylate anionic groups participated
in Ca binding. Conjugation with taurine almost completely prevented this
Ca-dependent precipitation. Intravenous infusion of SGLC (12 mumol/h) in
unanesthetized rats with permanent biliary drainage induced cholestasis,
which was preceded by the formation of a biliary Ca-SGLC precipitate,
suggesting a causal relationship. Taurine conjugation prevented this
biliary precipitation as well as cholestasis. Furthermore, we studied in
vitro the binding of the sulfated bile acids to insoluble calcium
phosphate, simulating interactions with Ca at the intestinal level.
Compared with STLC, micellar SGLC was bound with much higher affinity. This
high-affinity binding was probably due to the involvement of both the
sulfate and the carboxylate group. This might also explain that the
apparent critical micellar concentration of SGLC, in contrast to that of
STLC, was extremely Ca dependent. The present findings indicate that 1)
interaction with calcium might be responsible for the differential
cholestatic properties of SGLC and STLC and 2) binding of sulfated
lithocholic acid conjugates to insoluble calcium phosphate in the
intestinal lumen is likely to prevent their accumulation in the
enterohepatic circulation.
