Cyclic AMP independent inhibition of platelet aggregation by prostaglandin E1 is mediated through factor Xa.
Normal plasma exposed to an insolubilized omega-NH2-hexyl-agarose derivative of PGE1 inhibits ADP-induced platelet aggregation. To define the plasma macromolecule responsible, we tested plasma congenitally deficient in coagulation factors for this property. Only plasma deficient in factor X failed to inhibit platelet aggregation under these conditions. The inhibition could be restored by reconstituting the defective plasma with bovine or human factor X. Purified factor X or Xa exposed to insolubilized PGE1 also inhibited ADP-induced platelet aggregation. Factor Xa could reverse suggesting that factor Xa was the responsible component. This conclusion was further supported by the ability of heparin to reverse the inhibitory effect of altered factor Xa when the anticoagulant was added simultaneously to platelets. The results were not due to the release of PGE1 from the insoluble derivative. Factor Xa may have a heretofore unrecognized effect on modulating platelet functions.
D000527:Alprostadil / Q000031:analogs & derivatives; D000925:Anticoagulants; D000242:Cyclic AMP / Q000502:physiology; D004791:Enzyme Inhibitors; D005170:Factor X / Q000502:physiology*; D005171:Factor X Deficiency / Q000097:blood; D015951:Factor Xa; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000502:physiology*; D011459:Prostaglandins E, Synthetic / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins; D012685:Sepharose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013735:Testicular Hormones / Q000494:pharmacology
D000925:Anticoagulants; D004791:Enzyme Inhibitors; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D011506:Proteins; D013735:Testicular Hormones; C039421:prostaglandin E1-hexyl-sepharose; C039579:testicular anticoagulant protein, Bos taurus; D005170:Factor X; D006493:Heparin; D012685:Sepharose; D000242:Cyclic AMP; D015951:Factor Xa; D000527:Alprostadil