title: Effect of PP1D-1, a synthetic antiplatelet compound, on rabbit platelets.
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 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 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.
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
authors.forename: C H
authors.initials: CH
authors.lastname: Liao
authors.forename: F N
authors.initials: FN
authors.lastname: Ko
authors.forename: S C
authors.initials: SC
authors.lastname: Kuo
authors.forename: C M
authors.initials: CM
authors.lastname: Teng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000096:biosynthesis / Q000097:blood; D006152:Cyclic GMP / Q000096:biosynthesis / Q000097:blood; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis / Q000097:blood; D009285:Naphthoquinones / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000096:biosynthesis / Q000097:blood; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
chemical_list: C104871:2-chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone; D009285:Naphthoquinones; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D006152:Cyclic GMP; D015230:Prostaglandin D2; D002118:Calcium