Effect of PP1D-1, a synthetic antiplatelet compound, on rabbit platelets

The antiplatelet mechanism of a synthetic compound, 2-chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D-1), was studied by employing washed rabbit platelets in vitro. PP1D-1 concentration-dependently inhibited thrombin (0.1 U/ml)-, platelet-activating factor (2 ng/ml)-, collagen (10 μg/ml)-, arachidonic acid (100 μM)- and U46619 (1 μM)-induced aggregation and ATP release in washed rabbit platelets. The IC₅₀ values of PP1D-1 for aggregation induced by the above inducers are 17.9 ± 1.7, 9.8 ± 1.1, 3.9 ± 0.4, 1.8 ± 0.3 and 1.7 ± 0.3 μM, respectively. PP1D-1 did not affect platelet thromboxane B₂ or prostaglandin D₂ formation induced by arachidonic acid, indicating that it did not affect cyclooxygenase and thromboxane synthase activities. PP1D-1 significantly inhibited the formation of inositol 1,4,5-trisphosphate caused by these five platelet stimulators. Moreover, PP1D-1 inhibited the increase in intracellular calcium concentration induced by these agents. On the contrary, PP1D-1 did not inhibit thapsigargin-elevated intracellular calcium concentration in indomethacin-pretreated platelets, indicating it did not influence the effect of thapsigargin. According to these data, PP1D-1 exerts antiplatelet effects mainly by inhibiting phosphoinositide turnover.