AJP - Gastrointestinal and Liver Physiology, Vol 257, Issue 3 371-G379, Copyright © 1989 by American Physiological Society
Ursodeoxycholate-induced changes in hepatic Na+-H+ exchange and biliary HCO3- excretion
M. S. Anwer, M. K. Hondalus and J. M. Atkinson
Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536.
Ursodeoxycholate (UDC)-induced HCO3- -rich choleresis may be due to
activation of sinusoidal Na+-H+ exchange followed by an increase in
intracellular pH (pHi) and HCO3- excretion via canalicular Cl- -HCO3-
exchange. To test this hypothesis, we studied the effect of UDC and
tauroursodeoxycholate (TUDC) on net H+ efflux from perfused rat livers and
pHi in isolated hepatocytes in the presence and absence of amiloride.
UDC-induced increases in biliary HCO3- concentration and excretion were
inhibited by amiloride. However, these increases were temporally associated
with an initial decline in H+ efflux and pHi followed by a gradual recovery
toward base line. The initial decline in H+ efflux was associated with a
rapid uptake of UDC. Amiloride inhibited only the recovery phases of H+
efflux and pHi. TUDC increased amiloride-sensitive H+ efflux without
affecting biliary [HCO3-] and decreased pHi in the presence but not in the
absence of amiloride. Amiloride decreased TUDC-induced choleresis and HCO3-
excretion most likely by decreasing TUDC excretion. TUDC decreased biliary
[Cl-] and increased hepatic O2 uptake more than UDC. We conclude that a
rapid influx of UDC in the protonated form decreases pHi and net H+ efflux
initially. The recovery phase is due to Na+-H+ exchange activated by
decreased pHi and possibly by UDC and increased cellular respiration. TUDC
indirectly stimulates Na+-H+ exchange most likely by increasing cellular
respiration. UDC-induced HCO3- -rich choleresis, which is observed at a
time when both net H+ efflux and pHi are less than control values, is
unlikely to be due to a direct activation of Na+-H+ exchange.
