Inhibition by warfarin of liver microsomal vitamin K-reductase in warfarin-resistant and susceptible rats.
Biochem Pharmacol
; 33(8): 1331-6, 1984 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-6712738
ABSTRACT
The NADH-dependent vitamin K-reductase activity of liver microsomes from three closely related rat strains has been studied. One strain (TAS) is susceptible and two strains (HW and HS) resistant to the anticoagulant and lethal effects of warfarin. The effects of cofactors, temperature, detergent and dithiothreitol on vitamin K1 reduction and solvent extraction of substrate and product have been investigated. Vitamin K-reductase activity was inhibited by approximately 13 and 8% respectively when microsomal preparations from TAS and HW animals were incubated with 50 microM vitamin K1 and 10 microM warfarin. In HS rat liver microsomes the enzyme was highly resistant to inhibition by warfarin. Evidence is presented and discussed that suggests that NADH-dependent vitamin K-reductase may be inhibited in the anticoagulant effect of warfarin and may be altered as a result of expression of the warfarin-resistance gene in HS rats. The enzyme activity studied was probably not a DT-diaphorase although both NADH and NADPH acted as cofactors for the reaction.
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Base de dados:
MEDLINE
Assunto principal:
Quinona Redutases
/
Varfarina
/
Microssomos Hepáticos
/
NADH NADPH Oxirredutases
Limite:
Animals
Idioma:
En
Ano de publicação:
1984
Tipo de documento:
Article