Response of human platelets to inhibition of thromboxane synthesis

Abstract

The behaviour of human platelets was studied by mechanical induced platelet aggregation under inhibition of different enzymes of the arachidonic acid metabolism. Platelet aggregation was followed by the release of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2). The cyclooxygenase inhibitor indomethacin suppressed the generation of both arachidonic acid metabolites simultaneously with the platelet aggregation. Imidazole or OKY-1581 inhibited the aggregation induced synthesis of TXB2 in a dose dependent manner whereas the PGE2 synthesis increased. After selective inhibition of endogenous TXB2 generation by imidazole or OKY-158l no correlation was found between platelet aggregation and thromboxane synthesis in platelet rich plasma. These results are in contrast to the general concept that platelet aggregation is mediated by TXA2. It is concluded that TXA2 is not essential for all sorts of platelet activation.