Amiloride and taurine inhibit cholate-induced HCO3(-)-rich choleresis in perfused rat livers.
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.
Anwer
M S
MS
Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536.
Atkinson
J M
JM
Zimniak
P
P
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D013654:Taurine / Q000494:pharmacology*; D013656:Taurocholic Acid / Q000494:pharmacology
D001639:Bicarbonates; D001647:Bile Acids and Salts; D002793:Cholic Acids; D013654:Taurine; D013656:Taurocholic Acid; D000584:Amiloride; D019826:Cholic Acid