Ko F N, Wu T S, Lu S T, Wu Y C, Huang T F, Teng C M
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Thromb Res. 1989 Oct 15;56(2):289-98. doi: 10.1016/0049-3848(89)90170-9.
Protopine inhibited the aggregation and ATP release of rabbit platelets induced by ADP, arachidonic acid, PAF, collagen and ionophore A23187. Although the platelet aggregation caused by thrombin was not inhibited by protopine (100 micrograms/ml), the release reaction was partially suppressed. In rabbit platelet-rich plasma, protopine also inhibited the platelet aggregation caused by ADP, arachidonic acid, PAF and collagen. The thromboxane B2 formation of washed platelets caused by arachidonic acid, collagen, ionophore A23187 and thrombin was suppressed by protopine. Protopine inhibited the intracellular calcium increase caused by arachidonic acid in quin-2/AM loaded rabbit platelets. In the presence of indomethacin, the intracellular calcium increase caused by collagen and PAF was completely suppressed by protopine, and the intracellular calcium increase caused by thrombin was partially inhibited. The phosphoinositides breakdown caused by collagen and PAF was inhibited by protopine, but that by thrombin was not affected significantly. Protopine did not cause the elevation of cyclic AMP level of platelets. It is concluded that the antiplatelet effects of protopine is due to inhibition on thromboxane formation and phosphoinositides breakdown and then lead to the decrease of intracellular calcium concentration.
原阿片碱抑制由ADP、花生四烯酸、血小板活化因子、胶原和离子载体A23187诱导的兔血小板聚集和ATP释放。虽然原阿片碱（100微克/毫升）不抑制凝血酶引起的血小板聚集，但释放反应受到部分抑制。在富含兔血小板的血浆中，原阿片碱也抑制由ADP、花生四烯酸、血小板活化因子和胶原引起的血小板聚集。原阿片碱抑制由花生四烯酸、胶原、离子载体A23187和凝血酶引起的洗涤血小板中血栓素B2的形成。原阿片碱抑制在负载喹吖因-2/AM的兔血小板中由花生四烯酸引起的细胞内钙增加。在吲哚美辛存在的情况下，由胶原和血小板活化因子引起的细胞内钙增加被原阿片碱完全抑制，由凝血酶引起的细胞内钙增加被部分抑制。由胶原和血小板活化因子引起的磷酸肌醇分解被原阿片碱抑制，但由凝血酶引起的磷酸肌醇分解未受到明显影响。原阿片碱不会引起血小板环磷酸腺苷水平升高。结论是原阿片碱的抗血小板作用是由于抑制血栓素形成和磷酸肌醇分解，进而导致细胞内钙浓度降低。
