Chang-Hui Liao (1), Feng-Ning Ko (1), Sheng-Chu Kuo (2) and Che-Ming
Teng (1,*)
(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