Effect of ursodeoxycholic acid on intracellular pH regulation in isolated rat bile duct epithelial cells

Am J Physiol. 1993 Oct;265(4 Pt 1):G783-91. doi: 10.1152/ajpgi.1993.265.4.G783.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Ammonium Chloride / pharmacology
  • Animals
  • Antiporters / metabolism
  • Bile Ducts / cytology
  • Bile Ducts / metabolism*
  • Chloride-Bicarbonate Antiporters
  • Chlorides / metabolism
  • Cholic Acid
  • Cholic Acids / pharmacology
  • Epithelial Cells
  • Epithelium / metabolism
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Intracellular Membranes / metabolism*
  • Rats
  • Sodium-Hydrogen Exchangers / metabolism
  • Taurochenodeoxycholic Acid / pharmacology
  • Ursodeoxycholic Acid / pharmacology*

Substances

  • Antiporters
  • Chloride-Bicarbonate Antiporters
  • Chlorides
  • Cholic Acids
  • Sodium-Hydrogen Exchangers
  • Ammonium Chloride
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine
  • Ursodeoxycholic Acid
  • Cholic Acid