Effect of ursodeoxycholic acid on intracellular pH regulation in isolated rat bile duct epithelial cells
Alvaro, D.; Mennone, A.; Boyer, J.L.
American Journal of Physiology 265(4 Pt 1): G783-G791
1993
ISSN/ISBN: 0002-9513 PMID: 8238362 Document Number: 422143
To determine if ursodeoxycholic acid (UDCA) induces a HCO-3--rich hypercholeresis by stimulating HCO-3- secretion from bile duct epithelial (BDE) cells, we studied the effect of UDCA, sodium tauroursodeoxycholate (TUDCA), and cholic acid on intracellular pH (pH-i) regulation and HCO-3- 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 (pH-u)), 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 HCO-3-. In contrast, TUDCA (1 mM) had no effect on pH-i in either media. BDE acidification induced by UDCA (1.5 mM) in KRB was not inhibited by Cl- depletion excluding activation of Cl--HCO-3-exchange. Most BDE cells spontaneously recovered their basal pH-i during the UDCA infusion (0.5-1 mM) by a secondary activation of the Na+-H+ exchanger (amiloride inhibition of pH-i recovery; n = 4), and pH-i overshot basal levels by 0.1-0.2 pH-u after UDCA withdrawal. The activity of Cl--HCO-3- exchange (Cl- removal/readmission maneuver) as well as the activities of Na+-H+ exchange and Na+-HCO-3- symport (NH-4Cl 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 HCO-3- excretion from isolated rat BDE cells but modifies pH-i in BDE cells as a weak acid.