AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 3 453-G461, Copyright © 1990 by American Physiological Society
Amiloride and taurine inhibit cholate-induced HCO3(-)-rich choleresis in perfused rat livers
M. S. Anwer, J. M. Atkinson and P. Zimniak
Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536.
Bile acid-induced HCO3(-)-rich choleresis may be due to primary activation
of sinusoidal Na(+)-H+ exchange or to biliary reabsorption of unconjugated
bile acid. To test these hypotheses, we studied the effect of cholate and
taurocholate (TC) (infused at 10 mumol/min for 20 min) on net H+ efflux,
biliary [HCO3-], and bile flow in perfused rat livers and on intracellular
pH (pHi) in isolated hepatocytes. Cholate, but not TC, produced
HCO3(-)-rich choleresis. Amiloride and taurine decreased cholate-induced
choleresis and HCO3- excretion and biliary excretion of unconjugated
cholate. Amiloride, but not taurine, decreased cholate-induced net H+
efflux. Both cholate and TC (200-750 microM) decreased pHi. Cholate was
metabolized to a polar compound, most likely cholate glucuronide, in the
presence of amiloride. These results are consistent with the hypothesis
that the biliary reabsorption of unconjugated cholate may be involved in
HCO3(-)-rich choleresis. Amiloride also inhibited net hepatic uptake and
biliary excretion of cholate and TC without affecting hepatic content of
bile acids. It is suggested that amiloride may decrease the maximal
excretion rate of cholate and TC. Since cholate and TC induce
amiloride-sensitive net H+ efflux and decrease pHi, it appears that cholate
and TC activate Na(+)-H+ exchange indirectly by decreasing pHi.
