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

@article{Moncada1976AnEI,
  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},
  journal={Nature},
  year={1976},
  volume={263},
  pages={663-665}
}
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… 
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References

SHOWING 1-10 OF 20 REFERENCES
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
Prostaglandin endoperoxides IX. Characterization of rabbit aorta contracting substance (RCS) from guinea pig lung and human platelets.
TLDR
Material causing contraction of the isolated rabbit aorta was released from guinea pig lung following perfusion with arachidonic acid and from human blood platelets after addition of thrombin to induce aggregation and quantitative analyses of the endoperoxides released from the lungs and platelets showed that only a minor part of the rabbit aORTa contracting activity was due to the prostaglandin end operoxides.
Physiological role of an endoperoxide in human platelets: hemostatic defect due to platelet cyclo-oxygenase deficiency.
TLDR
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.
TLDR
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
TLDR
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
TLDR
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.
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
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