Effect of inhibition of protein synthesis on cholestasis induced by taurolithocholate, lithocholate, and a manganese-bilirubin combination in the rat.
Taurolithocholate, lithocholate, and a manganese-bilirubin combination produced a rapid reduction in bile flow after i.v. injection in the rat. The effect was diminished or blocked completely by pretreating the animals with cycloheximide or ethionine, known inhibitors of protein synthesis. The injection sequence and time period between administration of the inhibitor of protein synthesis and the cholestatic agent influenced the degree to which they modulated the cholestatic effect. The results indicate that uninterrupted protein synthesis is required for the expression of maximal reduction of bile flow by taurolithocholate, lithocholate, and a manganese-bilirubin combination.
Dahlström-King
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Département de pharmacologie, Faculté de médecine, Université de Montréal, Québec, Canada.
Plaa
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GL
D000818:Animals; D001663:Bilirubin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002779:Cholestasis / Q000139:chemically induced* / Q000517:prevention & control; D003513:Cycloheximide / Q000494:pharmacology; D004195:Disease Models, Animal; D008095:Lithocholic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013658:Taurolithocholic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013997:Time Factors
D011500:Protein Synthesis Inhibitors; D008345:Manganese; D013658:Taurolithocholic Acid; D008095:Lithocholic Acid; D003513:Cycloheximide; D001663:Bilirubin