TXA2-antagonistic properties of agents affecting prostaglandin synthesis or the cyclic nucleotide system in human platelets.

Abstract

Prostaglandins (PG) E1 and E2 as well as 3-isobutyl-1-methylxanthine, nitroprusside, dibutyryl cyclic AMP and N-0164 inhibited platelet aggregation induced by the thromboxane (TX) A2-mimetic prostaglandin endoperoxide analogue U46619. Non-steroidal anti-inflammatory agents - acetylsalicylic acid, indomethacin, tolfenamic acid, flumizole, nictindole and proquazone - did not demonstrate any antagonistic actions on U46619-induced aggregation at concentrations causing inhibition of prostaglandin/thromboxane synthesis-dependent forms of platelet aggregation. Comparing with the effects of the different test substances on ADP-or arachidonic acid-induced platelet aggregation, it can be suggested that PGE2 as well as 3-isobutyl-1-methylxanthine, nitroprusside, and dibutyryl cyclic AMP are functional antagonists and N-0164 is a receptor level antagonist of TXA2 in platelets.