An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation

  title={An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation},
  author={Salvador Moncada and Richard J. Gryglewski and Stuart Bunting and John Robert Vane},
Microsomes prepared from rabbit or pig aortas transformed endoperoxides (PGG2 or PGH2) to an unstable substance (PGX) that inhibited human platelet aggregation. PGX was 30 times more potent in this respect than prostaglandin E1. PGX contracted some gastrointestinal smooth muscle and relaxed certain isolated blood vessels. Prostaglandin endoperoxides cause platelet aggregation possibly through the generation by platelets of thromboxane A2. Generation of PGX by vessel walls could be the… 
Inhibition of platelet aggregation by a placental substance with prostacyclin-like activity
The ability of normal placental tissue to generate a labile substance which has the ability to inhibit ADP-induced platelet aggregation is demonstrated.
The Inhibitory Effect of Aspirin on Platelet and Vascular Prostaglandins in Rats cannot be Completely Dissociated
The rationale for clinical use of this drug in thrombosis prevention trials is questionable and treatment schedules would have to be calibrated to inhibit proaggregating platelet prostaglandins and TXA2 without affecting protective vascular prostaglandsins (PGI2).
Prostacyclin and Thromboxane A2 in Platelet Vessel Wall Interactions
Prostacyclin was originally found as a product of the conversion of prostaglandin endoperoxides by a microsomal enzyme from blood vessels and was later chemically identified as an intermediate in the formation of 6-oxo- PGF,1α compound.
Thromboxane A2, Prostacyclin and Aspirin: Effects
It has been suggested but not yet established that low doses of aspirin preferentially inhibit TxA2 biosynthesis, and therefore prevents the subsequent production of TXA2, PGI2 and other prostaglandins.
Blood platelets do not provide endoperoxides for vascular prostacyclin production
Results are reported indicating that it is highly unlikely that blood platelets are able to promote vascular prostacyclin formation by supplying cyclic endoperoxides.


Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides
The microsomal fraction of horse and human platelets contains an enzyme which converts prostaglandin cyclic endoperoxides (PGG2 or PGH2) to a substance which is much more potent in contracting strips
Physiological role of an endoperoxide in human platelets: hemostatic defect due to platelet cyclo-oxygenase deficiency.
It is concluded that the endoperoxide (PGG2) is essential in normal hemostasis because of its role in initiating the release reaction required for aggregation by collagen and the second wave of aggregation caused by, e.g., ADP.
Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides.
Evidence is presented that the more unstable and major component of rabbit aorta contracting substance (RCS) formed in platelets and guinea pig lung is also thromboxane A2.
Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis.
  • M. Hamberg, B. Samuelsson
  • Chemistry, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1973
The smooth muscle-stimulating activity of the endoperoxide ester on the isolated rabbit aortas trip was 4- to 8-times higher than that of the methyl ester of prostaglandin E(2).
Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets.
  • M. Hamberg, B. Samuelsson
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1974
The almost exclusive transformation of the endoperoxide structure into non-prostaglandin derivatives supports the hypothesis that the end operoxides can participate directly and not by way of the classical prostaglandins in regulation of cell functions.
Effects of Platelet Transfusions: Plug Formation and Maintenance of Vascular Integrity
  • A. Roy, I. Djerassi
  • Biology, Medicine
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
  • 1972
Since endothelial changes appear to account for initiating spontaneous bleeding and lack of hemostatic plug formation for its continuation, various programs of platelet replacement may be needed by thrombocytopenic individuals requiring prophylactic or therapeutic platelet transfusions.
Ultrastructural changes of endothelium associated with thrombocytopenia.
In a study of the relationship between thrombocytopenia and increased vascular fragility, changes in the endothelium of capillaries and postcapillary venules of the tongue were examined by electron