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Cyclic AMP inhibits synthesis of prostaglandin endoperoxide (PGG2) in human platelets

1976; Elsevier BV; Volume: 68; Issue: 2 Linguagem: Inglês

10.1016/0006-291x(76)91183-9

1090-2104

Curt Malmsten, Elisabeth Granström, Bengt Samuelsson,

Eicosanoids and Hypertension Pharmacology

Dibutyryl-cAMP but not dibutyryl-cGMP inhibited platelet aggregation and release of 14C-serotonin and ADP when induced by collagen and arachidonate but not when induced by the endoperoxide PGG2* (TXB2) induced by addition of collagen to platelet rich plasma (PRP) was decreased by dibutyryl-cAMP and agents known to increase the concentration of cAMP (PGE1, PGD2, theophylline and acetyl choline). PGE2 in concentrations known to decrease cAMP levels increased the formation of TXB2 whereas concentrations of PGE2 known to increase cAMP levels decreased the amount of TXB2 formed. That this was due to an effect on the cyclooxygenase was indicated by inhibition of the transformation of arachidonic acid by DB-cAMP and by high concentrations of PGE2. Additional support for regulation of the cyclo-oxygenase by cAMP and its relevance to platelet aggregation was obtained by demonstrating stimulation of PGG2 induced aggregation by low concentrations of PGE2 and the absence of this effect in the presence of a cyclo-oxygenase inhibitor.