Prostaglandin H2 directly lowers human platelet cAMP levels

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.