AJP - Gastrointestinal and Liver Physiology, Vol 265, Issue 4 783-G791, Copyright © 1993 by American Physiological Society
Effect of ursodeoxycholic acid on intracellular pH regulation in isolated rat bile duct epithelial cells
D. Alvaro, A. Mennone and J. L. Boyer
Department of Internal Medicine, Yale University, School of Medicine, New Haven, Connecticut 06510.
To determine if ursodeoxycholic acid (UDCA) induces a HCO3(-)-rich
hypercholeresis by stimulating HCO3- secretion from bile duct epithelial
(BDE) cells, we studied the effect of UDCA, sodium tauroursodeoxycholate
(TUDCA), and cholic acid on intracellular pH (pHi) regulation and HCO3-
excretion in BDE cells isolated from normal rat liver. Exposure of BDE
cells to UDCA (0.5-1.5 mM) produced a dose-dependent initial acidification
[from -0.05 to -0.16 pH units (pHu)], which was lower in Krebs-Ringer
bicarbonate than in N-2-hydroxyethylpiperazine-N'-2- ethanesulfonic acid
(HEPES), because of the higher cell-buffering power in the presence of
HCO3-. In contrast, TUDCA (1 mM) had no effect on pHi in either media. BDE
acidification induced by UDCA (1.5 mM) in KRB was not inhibited by Cl-
depletion excluding activation of Cl(-)-HCO3- exchange. Most BDE cells
spontaneously recovered their basal pHi during the UDCA infusion (0.5-1 mM)
by a secondary activation of the Na(+)-H+ exchanger (amiloride inhibition
of pHi recovery; n = 4), and pHi overshot basal levels by 0.1-0.2 pHu after
UDCA withdrawal. The activity of Cl(-)-HCO3- exchange (Cl-
removal/readmission maneuver) as well as the activities of Na(+)-H+
exchange and Na(+)-HCO3- symport (NH4Cl acid load in HEPES and KRB,
respectively) were unaffected by UDCA (0.5 mM) compared with controls.
Cholic acid (1.5 mM), which does not produce a hypercholeresis, also
acidified BDE cells in KRB media. These studies indicate that UDCA does not
stimulate HCO3- excretion from isolated rat BDE cells but modifies pHi in
BDE cells as a weak acid.
