Effect of PP1D-1, a Synthetic Antiplatelet Compound, on Rabbit Platelets

The Japanese Journal of Pharmacology

Feng-Ning Ko¹  Chang-Hui Liao¹  Sheng-Chu Kuo²  Che-Ming Teng¹ 

[1] Pharmacological Institute, College of Medicine, National Taiwan University;Graduate Institute of Pharmaceutical Chemistry, China Medical College

关键词: 2-Chloro-3-methoxycarbonylpropionamido-1;    4-naphthoquinone (PP1D-1);    Platelet (rabbit);    Inositol 1;    4;    5-trisphosphate (IP3);    Intracellular calcium concentration;    Thapsigargin;   

DOI  :  10.1254/jjp.76.141

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(28)Cited-By(4)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.

【 授权许可】

Unknown