Prostacyclin increases cyclic AMP levels and adenylate cyclase activity in platelets (original) (raw)

Nature volume 267, pages 850–852 (1977) Cite this article

Abstract

PROSTACYCLIN (PGX) (ref. 1) is the name proposed for the metabolic product of a recently discovered enzymic transformation of the prostaglandin endoperoxides PGG2 and PGH2 (refs 2–4). Prostacyclin synthetase, the enzyme which catalyses this conversion, is particularly active in the microsomal fraction of blood vessel walls3,4 although there is evidence that it is also present in the rat stomach fundus3. The prostaglandin endoperoxides, PGG2 and PGH2, have been shown to contract arterial smooth muscle and to cause platelet aggregation5,6, whereas, in contrast, prostacyclin relaxes arterial strips and prevents platelets aggregation3. A biochemical interaction has therefore been postulated to exist between platelets and the blood vessels wall, such that endoperoxides derived from platelets are converted by the vessel wall into prostacylin, which in turn actively prevents the deposition of platelets on the vascular endothelium2,4. In general, agents which inhibit platelet aggregation, such as PGE1, increase cyclic AMP levels, whereas agents causing aggregation lower platelet cyclic AMP levels7. The ability of prostacyclin to rapidly reverse or prevent platelet aggregation suggested that its action on the platelet might, like that of PGE1, be mediated by an increase in cyclic AMP levels. This hypothesis is supported by the experiments detailed here which strongly suggest that prostacyclin generated by incubation of arachidonic acid, platelets and aortic tissue, causes a rapid and pronounced accumulation of cyclic AMP by intact platelets, as well as stimulation of adenylates cyclase in isolated platelet membranes.

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Authors and Affiliations

  1. Departments of Chemical Pathology and Haematology, Academic Division of Pathology, University of Sheffield Medical School, Sheffield, UK
    L. C. BEST, T. J. MARTIN, R. G. G. RUSSELL & F. E. PRESTON

Authors

  1. L. C. BEST
  2. T. J. MARTIN
  3. R. G. G. RUSSELL
  4. F. E. PRESTON

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BEST, L., MARTIN, T., RUSSELL, R. et al. Prostacyclin increases cyclic AMP levels and adenylate cyclase activity in platelets.Nature 267, 850–852 (1977). https://doi.org/10.1038/267850a0

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