Substances that increase the cyclic AMP content prevent platelet aggregation and the concurrent release of pharmacologically active substances evoked by arachidonic acid.
Arachidonic acid-induced platelet aggregation was inhibited by prostaglandins E1 and F2alpha(PGE1 and PGF2alpha), papaverine and dibutyryl cycle AMP. Prostaglandin E2 displayed a biphasic effect, as concentrations below 2 muM potentiated aggregation, whereas concentrations above it were inhibitory. Isoproterenol (up to 10 mM) failed to block aggregation but inhibition was uncovered in presence of adrenergic alpha-blocking agents. Isoproterenol potentiated aggregation due to sub-threshold amounts of arachidonic acid, and this effect, but not that due to PGE2, was suppressed by the alpha-blocking agents. Isoproterenol and PGE2 appear thus to enhance arachidonic acid-induced platelet aggregation after interacting with different receptor sites. The yield of rabbit aorta contracting activity formed during AA-induced aggregation was markedly reduced by PGE1, dibutyryl cyclic AMP and high concentrations of PGE2, and was increased by low concentrations of the latter. PG-like activity was not significantly reduced when aggregation and generation of rabbit aorta contracting activity were inhibited by bibutyryl cyclic AMP. It is hypothesized that interaction of human platelets and arachidonic acid results in formation of different pharmacologically active materials, possibley bearing similar lipoperoxide structures. Generation of one portion of these materials is controlled by the adenyl cyclase-cyclic AMP system, whereas another portion, that comprises the natural PG, is cyclic AMP-independent. Prostaglandins formed during platelet aggregation have a regulatory role and modulate the platelet response, rather than constitute a trigger stimulus for aggregation.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001095:Arachidonic Acids / Q000494:pharmacology*; D003994:Bucladesine; D000242:Cyclic AMP / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010208:Papaverine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011817:Rabbits; D013189:SRS-A / Q000494:pharmacology; D013268:Stimulation, Chemical
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013189:SRS-A; D003994:Bucladesine; D010208:Papaverine; D000242:Cyclic AMP