title: Prostaglandin H2 directly lowers human platelet cAMP levels.
abstract: In the present study we investigated the ability of prostaglandin H2 (PGH2) to lower platelet cAMP levels independent of thromboxane A2 (TXA2) production. Human platelet-rich plasma was incubated (37 degrees C) with 13 nM prostacyclin (PGI2) to increase platelet cAMP levels. Addition of 500 microM arachidonic acid (AA) to PGI2-treated platelets resulted in a return of cAMP to control levels. Inhibition of both PGH2 and TXA2 production with indomethacin (20 microM) blocked the ability of AA to lower PGI2-stimulated increases in cAMP. On the other hand, selective inhibition of TXA2 production with the thromboxane synthetase blocker 7-(1 imidazoyl) heptanoic acid (7-IHA; 10 microM), did not prevent the cAMP lowering effect of added AA. These results provide evidence that PGH2 need not be converted to TXA2 in order to reduce platelet cAMP levels.
mesh_terms: D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D000242:Cyclic AMP / Q000097:blood*; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011449:Prostaglandin Endoperoxides / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000097:blood
chemical_list: D001095:Arachidonic Acids; D007093:Imidazoles; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D013928:Thromboxane A2; C024335:1-(7-carboxyhexyl)imidazole; D011464:Epoprostenol; D000242:Cyclic AMP; D007213:Indomethacin