Inhibitory Effects of TA-993 and Its Metabolite MB3 on Platelet Activation Induced by Collagen and U-46619 in Human Platelets

Abstract

In the present study, we investigated the effects of TA-993 and its metabolite MB3 on platelet activation in vitro. TA-993 and MB3 concentration-dependently inhibited platelet aggregation and ATP release induced by collagen in human platelets. Thromboxane (Tx) A₂ formation, as determined by the production of TxB₂, and the increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i) were also suppressed by TA-993 and MB3. TA-993 and MB3 did not inhibit TxA₂ formation caused by arachidonic acid. These results suggest that the inhibition of platelet activation by TA-993 and MB3 is partly mediated by an inhibition of TxA₂ formation at a step prior to cyclooxygenase. Furthermore, TA-993 and MB3 inhibited U-46619-induced platelet aggregation without blockade of the increase in [Ca²⁺]_i, suggesting that they are likely to exert some additional effects on the intracellular events induced by Ca²⁺.