Inhibition by warfarin of liver microsomal vitamin K-reductase in warfarin-resistant and susceptible rats

Biochemical Pharmacology
A D MacNicollM G Townsend


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.


Dec 1, 1973·FEBS Letters·C LindA D Martin
Aug 19, 1967·Nature·J H Greavses, P Ayres
Jan 15, 1982·Biochemical and Biophysical Research Communications·M J Fasco, L M Principe
Dec 31, 1980·Biochemical and Biophysical Research Communications·M J Fasco, L M Principe


Jan 1, 1987·Reviews on Drug Metabolism and Drug Interactions·F A SutcliffeG G Gibson
Mar 1, 1987·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J W Suttie
Jan 20, 2006·Journal of Biochemical and Molecular Toxicology·Romain LasseurEtienne Benoit

Related Concepts

Drug Resistance
Microsomes, Liver
NADH, NADPH Oxidoreductases
Menaquinone Reductases
Rats, Laboratory
In Vitro [Publication Type]

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Lipidomics & Rhinovirus Infection

Lipidomics can be used to examine the lipid species involved with pathogenic conditions, such as viral associated inflammation. Discovered the latest research on Lipidomics & Rhinovirus Infection.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Torsion Dystonia

Torsion dystonia is a movement disorder characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Here is the latest research.

Generating Insulin-Secreting Cells

Reprogramming cells or using induced pluripotent stem cells to generate insulin-secreting cells has significant therapeutic implications for diabetics. Here is the latest research on generation of insulin-secreting cells.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.

Epigenome Editing

Epigenome editing is the directed modification of epigenetic marks on chromatin at specified loci. This tool has many applications in research as well as in the clinic. Find the latest research on epigenome editing here.