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

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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)A_2 formation, as determined by the production of TxB_2, and the increase in intracellular Ca^2+ concentration ([Ca^2+]_i) were also suppressed by TA-993 and MB3, TA-993 and MB3 did not inhibit TxA_2, 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 TxA_2 formation at a step prior to cyclooxygenase. Furthermore, TA-993 and MB3 inhibited U-46619-induced platelet aggregation without blockade of the increase in [Ca^2+]_i, suggesting that they are likely to exert some additional effects on the intracellular events induced by Ca^2+.
公益社団法人日本薬学会の論文
2001-05-01