Prostacyclin increases cyclic AMP levels and adenylate cyclase activity in platelets

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 walls^3,4 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 aggregation^5,6, 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 endothelium^2,4. 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.