The inhibition of trapidil was proportionally to the concentration on human platelet aggregation, induced by ADP, collagen, arachidonic acid, thrombin and thromboxane A2. Furthermore, trapidil reversed aggregation once the process initiated (Fig. 1 (a)), and inhibited even primary aggregCtion induced by ADP. Subsequent experiments demonstrated trapidil inhibited ATP release from the aggregating platelets on Lumi-aggregometer examination.
So, we investigated the mode of inhibition of trapidil on platelet aggergation and release reaction induced by several inducers. The inhibition pattern was demonstrated that it was almost same on the release reaction, but somewhat different on ADP from the other inducers (Fig. 2).
Based on these findings, it was suggested that trapidil inhibited the lipid metabolism, which brought platelet release reaction. So, we measured the release of arachidonic acid and Tx-B2 biosynthesis in the aggregating platelets. Trapidil blocked completely Tx-B2 bio-synthesis with the concentration of 1mM, but did not show so much inhibition for the release of arachidonic acid as Tx-B2 biosynthesis, namely 39% with 1mM and 81% with 2mM.
Conclusively, trapidil inhibits the biosynthesis of Tx-B2 from arachidonic acid by inhibiting thromboxane synthetase (unpublished data). However, the inhibition of release reaction does not necessarily follow the inhibition of platelet aggregation.