Effects of Na+ replacement and amiloride on ursodeoxycholic acid-stimulated choleresis and biliary bicarbonate secretion.
In these studies, we have tested the hypothesis that bile acid-dependent bile formation is attributable, in part, to the stimulation of active bicarbonate secretion and have further explored the cellular mechanism(s) possibly involved in this process using the isolated perfused rat liver. Under control conditions, ursodeoxycholic acid (UDCA) infusion (3 mumol/min X 20 min) produced a 3.7-fold increase in bile flow and a 7.4-fold increase in HCO3- output. Amiloride (an inhibitor of Na+-H+ exchange) decreased UDCA-stimulated bile flow by 20.6% and decreased biliary HCO3- output by 24.9% but increased biliary UDCA output by 42.9%. Thus amiloride decreased UDCA choleretic efficiency (microliter UDCA-stimulated bile/mumol UDCA output) by 45% and UDCA-stimulated increase in HCO3- output per unit UDCA secreted by 48%. Substitution of Li+ for Na+ in perfusate virtually abolished (greater than 95% decrease) both the UDCA choleresis and increase in biliary HCO3- output but modestly decreased (39.6%) biliary bile acid output. Li+ substitution thus decreased UDCA choleretic efficiency by 98% and the UDCA-stimulated increase in HCO3- output by 96%. Amiloride had no effect and Li+ substitution produced a modest decrease in basal bile flow (26.0%) and HCO-3 output (33.5%). Neither amiloride nor Li+ substitution significantly affected UDCA uptake by cultured hepatocytes or by perfused liver. Amiloride (1 mM) also decreased taurocholate (TC)-stimulated choleresis by 48.5%, biliary TC output by 7.2%, and the choleretic efficiency of TC by 45%.(ABSTRACT TRUNCATED AT 250 WORDS)
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001646:Bile / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism / Q000502:physiology*; D013656:Taurocholic Acid / Q000494:pharmacology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D001639:Bicarbonates; D002712:Chlorides; D003840:Deoxycholic Acid; D013656:Taurocholic Acid; D014580:Ursodeoxycholic Acid; D000584:Amiloride; D008094:Lithium; D012964:Sodium; D011188:Potassium