GENERATION OF TXA2 IN HUMAN-PLATELET RICH PLASMA AND ITS INHIBITION BY NICTINDOLE AND PROSTACYCLIN

The aggregation of human platelets by adrenaline, adenosine diphosphate (ADP), arachidonic acid (AA), thrombin and collagen was studied in relation to thromboxane A2 (TXA2) formation in human platelet rich plasma (PRP). AA, thrombin and collagen-induced aggregation was associated with the release of TXA2. Adrenaline and ADP-induced aggregation has two phases and only the second irreversible phase was accompanied by TXA2 generation. A potent inhibitor of TXA2 synthetase-nictindole-inhibited both aggregation and TXA2 formation in platelets treated with AA, adrenaline and ADP (second phase). In collagen and thrombin-induced aggregation nictindole at low concentrations inhibited TXA2 formation but not aggregation. Prostacyclin suppressed aggregation and generation of TXA2 in PRP which was aggregated by all agents studied. Prostacyclin has no effect on activity of cyclo-oxygenase in disrupted platelets. It is concluded that TXA2 plays a supplementary role in all models of aggregation studied (perhaps except for AA-induced aggregation), while prostacyclin has a multidirectional anti-aggregating action. © 1979 The Italian Pharmacological Society.