REDUCTION BY ARACHIDONIC-ACID OF PROSTAGLANDIN-I2-INDUCED CYCLIC-AMP FORMATION - INVOLVEMENT OF PROSTAGLANDIN-E(2) AND PROSTAGLANDIN-F(2-ALPHA)

Arachidonic acid reverses the increase in cyclic AMP levels of washed human platelets exposed to prostaglandin (PG)I2, under conditions wher e the PGH2 analogue U46619 is ineffective. This effect of arachidonic acid was inhibited by aspirin, a cyclooxygenase inhibitor, but not by the thromboxane (Tx) synthase inhibitor Ridogrel, which induces, by in hibiting the conversion of PGH2 into TxA2, an overproduction of PGE2, PGD2 and PGF2alpha. Addition of PGE2 or PGF2alpha, which share a recep tor with PGI2, to Washed human platelets also induced a decrease in cy clic AMP levels, but PGD2, which interacts with a different receptor, had no effect. Thus neither PGD2, PGG2, PGH2, TxA2 nor TxB2 formed fro m arachidonic acid via the cyclooxygenase pathway is involved in the d ecrease in cyclic AMP levels. These findings were confirmed using fors kolin, a diterpene from the labdane family, which enhanced the formati on of cyclic AMP synergistically with the PGs. Also, arachidonic acid, unlike U46619, is able to reverse the inhibition of platelet aggregat ion by PGI2 after a lag phase of about 4 min. Our data indicate that a rachidonic acid decreased cyclic AMP levels through its cyclooxygenase metabolites PGE2 and PGF2alpha. probably interacting competitively wi th the receptor of PGI2. In addition, intracellular cyclic AMP levels and the degree of aggregation of platelets by arachidonic acid seem to be inversely correlated.