Platelet antithrombins: role of thrombin binding and the release of platelet fibrinogen.
The nature of platelet antithrombin was elucidated by comparison of thrombin binding and antithrombin activities of intact platelets and by purification of antithrombin from platelet lysates using glycerol osmotic lysis, ethanol precipitation and Sephadex gel filtration techniques. The major portion of the antithrombin and thrombin binding activity of intact platelets is lost after brief sonication. The antithrombin activity in destroyed platelets is found to be due to platelet fibrinogen. Treatment of platelets with PGE1 (100 microng/ml) markedly inhibits (greater than 80%) the release of platelet fibrinogen induced by thrombin. However, the PGE1 treatment produced slight (less than 30%) but significant decrease of antithrombin activity of intact platelets, whereas the binding of thrombin to platelets was not affected by PGE1 treatment. The amounts of thrombin bound to and inactivated by PGE1-treated platelets at the same cell concentration are identical. The above results suggest that platelets contain at least two antithrombin activities. One, which accounts for the major portion of platelet antithrombin is mediated by thrombin binding to platelets. The other, which attributes to a lesser extent to platelet antithrombin activity, is due to the release of platelet fibrinogen. Also, antithrombin is readily demonstrated in a plasma medium indicating physiological significance of platelet antithrombin.
D000991:Antithrombins / Q000378:metabolism*; D001665:Binding Sites; D001777:Blood Coagulation; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002458:Cell Fractionation; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D011458:Prostaglandins E / Q000494:pharmacology; D013010:Sonication / Q000009:adverse effects; D013917:Thrombin / Q000378:metabolism*
D000991:Antithrombins; D011458:Prostaglandins E; D005340:Fibrinogen; D013917:Thrombin