AJP - Gastrointestinal and Liver Physiology, Vol 247, Issue 1 112-G115, Copyright © 1984 by American Physiological Society
Calcium binding by lithocholic acid derivatives
D. G. Oelberg, W. P. Dubinsky, E. W. Adcock and R. Lester
Lithocholic acid (LCA) and its sulfate (LCS) and glucuronide (LCG)
derivatives are potent cholestatic agents. During the course of LCG-induced
cholestasis in rats, calcium (Ca) salts of LCG precipitate in bile. To
characterize the affinity of bile salts for Ca, solutions of selected bile
salts were titrated with Ca. Apparent equilibrium constants (KcaBS) were
determined from the unbound Ca ion concentrations that were measured
spectrophotometrically with metallochromic indicators antipyrylazo III or
murexide or with a Ca-selective electrode. KCaBS values were 1.12 +/- 0.04
X 10(-4) M for LCS, 2.88 +/- 0.26 X 10(-4) M for LCG, 3.09 +/- 0.21 X
10(-4) M for LCA, 1.93 +/- 0.07 X 10(-3) M for taurocholic acid (TC), 2.69
+/- 0.08 X 10(-3) M for glycocholic acid (GC), and 6.07 +/- 0.27 X 10(-3) M
for taurolithocholic acid sulfate (TLCS). The KCaBS for LCG measured by a
Ca-selective electrode under identical conditions was 5.53 +/- 2.75 X
10(-4) M. Comparing relative cholestatic potential with affinity for Ca,
cholestatic bile salts LCS, LCG, and LCA bind Ca 10-60 times more avidly
than TC, GC, and TLCS. At the unbound Ca ion concentrations of serum or
bile (approx 1 mM), only LCS, LCG, and LCA would be expected to bind
significant amounts of Ca.
