AJP - Gastrointestinal and Liver Physiology, Vol 251, Issue 2 189-G194, Copyright © 1986 by American Physiological Society
Intestinal absorption of lithocholic acid sulfates in the rat: inhibitory effects of calcium
F. Kuipers, H. Heslinga, R. Havinga and R. J. Vonk
Sulfation of lithocholic acid has been proposed as a mechanism for
elimination of this hepatotoxic bile acid from the body by accelerating its
fecal excretion. However, quantitative data on the absorption
characteristics of sulfated lithocholic acid conjugates in vivo are scarce.
We studied the intestinal absorption of 14C-labeled glycolithocholic acid
(GLC), taurolithocholic acid (TLC), and their 3 alpha-sulfate esters, SGLC
and STLC, respectively. Studies were performed in unanesthetized rats with
a permanent biliary drainage. At an intestinal infusion rate of 125
nmol/min, which is comparable to 7% of the normal biliary bile acid output
in the rat, the absorption of sulfated lithocholic acid conjugates was
delayed when compared with their unsulfated precursors but quantitatively
only slightly reduced over a 24-h period: SGLC 90.9 +/- 3.6%, GLC 94.4 +/-
1.1%, STLC 84.4 +/- 3.0%, and TLC 94.2 +/- 2.1%. Urinary excretion of
sulfated and unsulfated bile acids was similar and never exceeded 2% of the
dose. SGLC absorption was dose dependent, was not altered by coinfusion of
rat bile, and was only slightly reduced by a sixfold overdose of
taurocholic acid. SGLC and STLC were excreted into bile largely unchanged
in form. In contrast, GLC and TLC were extensively metabolized to more
polar bile acids, predominantly to beta-muricholic acid conjugates.
Replacement of NaCl in the infusion fluid by CaCl2 reduced the absorption
of SGLC and STLC by 63 and 52%, respectively. This calcium effect was less
pronounced for the unsulfated bile acids: GLC -22%, and TLC -19%.
Absorption of taurocholic acid was unaffected by CaCl2.(ABSTRACT TRUNCATED
AT 250 WORDS)
