Heparin-mediated neutralization of platelet antiaggregatory activity of prostacyclin (PGI2): studies on mechanism.
Prostacyclin (PGI2) is a well-known potent inhibitor of platelet aggregation. Its role has been implicated in physiological and pathological states of hemostasis. Heparin blocks the prostacyclin-mediated antiaggregatory activity on platelets. Prior treatment of heparin with heparinase as well as with protamine destroyed heparin's ability to neutralize PGI2. Studies on the mechanism of heparin blocking of PGI2 activity suggested that heparin interacted directly with PGI2, as shown by the loss of PGI2 mobility on thin layer chromatography concomitant with the loss of PGI2-mediated inhibition of platelet aggregation. PGI2 in this combination with heparin, nevertheless, retained its time-dependent ability to be hydrolyzed to 6-keto-PGF1 alpha. Findings of these studies may have implications in thrombosis and hemostasis, particularly in heparin-mediated abnormalities of circulating platelets.
D002855:Chromatography, Thin Layer; D003864:Depression, Chemical; D011464:Epoprostenol / Q000378:metabolism / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D019763:Heparin Lyase; D006801:Humans; D006868:Hydrolysis; D010974:Platelet Aggregation / Q000187:drug effects*; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology
D011479:Protamines; D006493:Heparin; D011464:Epoprostenol; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase