RT Journal Article
SR Electronic
T1 Warfarin Binding to Microsomes Isolated from Normal and Warfarin-Resistant Rat Liver
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 197
OP 203
VO 8
IS 2
A1 DAVID J. LORUSSO
A1 JOHN W. SUTTIE
YR 1972
UL http://molpharm.aspetjournals.org/content/8/2/197.abstract
AB A warfarin-binding site which had previously been demonstrated in liver microsomal membranes was studied. Although the binding site displayed apparently typical saturation binding curves when incubated with radioactive warfarin, the bound warfarin was not readily displaced by incubation with unlabeled warfarin. Warfarin-binding capacity was increased in membranes isolated from vitamin K-deficient rats, but was returned to normal when deficient rats were treated with 1 mg of phylloquinone on its chloro analogue. Prior treatment of animals with nonradioactive warfarin greatly decreased the subsequent binding capacity of the microsomal membranes in vitro. The warfarin-binding capacity was also very low in microsomes isolated from a strain of warfarin-resistant rats. The majority of the warfarin associated with the microsomal membranes isolated from warfarin-resistant rats was either bound very loosely or entrapped in vesicles, or it could be removed by phospholipase treatment. However, the warfarin associated with microsomal membranes from normal rats was bound to other membrane components, presumably protein.