Vitamin K and coumarin anticoagulants: dependence of anticoagulant effect on inhibition of vitamin K transport.
Coumarin anticoagulants inhibit the release of plasma clotting factor VII by vitamin K in liver slices from vitamin K-deficient animals without inhibition of protein synthesis. When the ratio of vitamin K to coumarin anticoagulant is kept constant, but the concentrations are increased, the inhibition disappears. This suggests that the pharmacological action of coumarin anticoagulants depends on irreversible inhibition of normal vitamin K transport to its site of action. At higher concentrations of vitamin K the inhibition can be surmounted, because vitamin K can enter the cell by an alternate route that is not inhibited by coumarin anticoagulants.
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001692:Biological Transport; D002247:Carbon Isotopes; D003374:Coumarins / Q000494:pharmacology*; D003864:Depression, Chemical; D005167:Factor VII / Q000378:metabolism*; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D010837:Vitamin K 1 / Q000037:antagonists & inhibitors; D014813:Vitamin K Deficiency / Q000378:metabolism*; D014859:Warfarin / Q000494:pharmacology
D000925:Anticoagulants; D002247:Carbon Isotopes; D003374:Coumarins; D014812:Vitamin K; D014859:Warfarin; D010837:Vitamin K 1; D005167:Factor VII; D007930:Leucine