Chang-Hui Liao (1), Feng-Ning Ko (1), Sheng-Chu Kuo (2) and Che-Ming
(1) Pharmacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Rd., Sect. 1, Taipei, Taiwan
(2) Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan
(*) To whom correspondence should be addressed.
Abstract: 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 microg/ml)-, arachidonic acid (100 microM)- and U46619 (1 microM)-induced aggregation and ATP release in washed rabbit platelets. The IC50values 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 microM, 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.
Keywords: 2-Chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D-1), Platelet (rabbit), Inositol 1,4,5-trisphosphate (IP3), Intracellular calcium concentration, Thapsigargin