Irreversible binding of 3-14C-antipyrine to hepatic protein in vivo and in metabolizing liver microsomes |
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Authors: | Sonja Tabarelli-Poplawski H. Uehleke |
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Affiliation: | (1) Institut für Pharmakologie der Universität Tübingen, Wilhelmstrasse 56, D-7400 Tübingen, Germany;(2) Abteilung für Toxikologie, Bundesgesundheitsamt, Thielallee 88/92, D-1000 Berlin 33 |
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Abstract: | Summary After i.p. injection of 3-14C-antipyrine (10 mole=1.9 mg with 10 Ci per 10 g of body weight) to mice radioactivity was irreversibly bound to liver proteins. The irreversible binding reached maximal values of 0.15 nmole/mg protein in liver microsomes after 30–60 min.During 60 min incubation with liver microsomes of mice and rabbits (phenobarbital pretreated) and a NADPH-regenerating system 3-14C-antipyrine was irreversibly bound to microsomal protein at a rate of 1.5 nmole/mg protein (mouse) and 3 nmole/mg protein (rabbit).In identical incubates with rabbit liver microsomes the 4-hydroxylation of antipyrine was 24 nmole/mg protein in 60 min and formaldehyde production from antipyrine 3 nmole/mg protein in 60 min.In incubates with rabbit liver microsomes the binding rate was 80–90% inhibited by 1mM metyrapone, SKF 525-A and trichloropropene epoxide respectively; 4-hydroxylation was 70–80% inhibited by the same substances. In the presence of 1 mM GSH, cysteine or ethylene diamine binding was 30–40% inhibited, whereas 4-hydroxylation showed no inhibition.Some of the results were presented at the 17th Spring Meeting of the Deutsche Pharmakologische Gesellschaft, Mainz, March 1976 |
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Keywords: | Antipyrine Metabolism Irreversible binding Liver microsomes |
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