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首页> 外文期刊>中国药理学报：英文版 >多种信号途径介导花生四烯酸与5-羟色胺在促人类血小板凝集中的协同作用
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多种信号途径介导花生四烯酸与5-羟色胺在促人类血小板凝集中的协同作用

机译：多种信号途径介导花生四烯酸与5-羟色胺在促人类血小板凝集中的协同作用

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AIM: To examine the signalling mechanisms involved in the synergistic interaction of 5-hydroxytryptamine (5-HT)and arachidonic acid (AA) in human platelet aggregation. METHODS: Blood was obtained from healthy human subjects, mixed with 3.8 % sodium citrate (9:1), and centrifuged to prepare platelet rich plasma (PRP). Aggregation was monitored using a Dual-channel Lumi-aggregometer. The agonist-induced influx of Ca2+ was measured using Fura-2 AM. TXA2 formation was studied using radiochemical method. RESULTS: Subthreshold concentration of 5-HT (2 μmol/L) potentiated the effect of low dose of AA (0.2 mmol/L) in human platelets. This synergistic effect was blocked by 5-HT2 receptor antagonist (methysergide IC50=5.2 nmol/L; cyproheptadine IC50=0.6 nmol/L), and thromboxane A2 receptor antagonist (SQ 29 548; IC50=30 nmol/L), showing that the effect is receptor-mediated.To examine the down-stream signalling pathways, we found that such an interaction was inhibited by calcium channel blockers (diltiazem; IC50=3 μmol/L and verapamil; IC50=5 μmol/L), phospholipase C (PLC) inhibitor (U73122;IC50=4 μmol/L), cyclooxygenase inhibitor, (indomethacin; IC50=0.2 μmol/L) and mitogen-activated protein (MAP)kinase inhibitor (PD98059; IC50=3 μmol/L). The effect was also inhibited by a specific tyrosine light chain kinase (TLCK) inhibitor, herbimycin A with IC50 value of 5 μmol/L. Pretreatment of platelet with 5-HT and AA induced rise in intracellular calcium and this effect was blocked by verapamil. CONCLUSION: The synergism between 5-HT and AA in platelet aggregation involves activation of PLC/Ca2+, COX, and MAP kinase pathways.
机译：目的：检查人体血小板聚集中5-羟基羟基胺（5-HT）和花生酸（AA）协同相互作用中涉及的信号传导机制。方法：从健康人对象中获得血液，与3.8％柠檬酸钠（9：1）混合，并离心以制备血小板富血浆（PRP）。使用双通道Lumi-aggregometer监测聚合。使用Fura-2 AM测量激动剂诱导的Ca2 +的流入。使用放射化学方法研究了TXA2的形成。结果：5-HT（2μmol/ L）的亚阈值浓度强调了低剂量Aa（0.2mmol / L）在人血小板中的作用。该协同效应被5-HT2受体拮抗剂（甲藻土合理IC50 = 5.2 Nmol / L;巯木庚嗪IC50 = 0.6 Nmol / L）障碍障碍物阻断，血液滤蛋A2受体拮抗剂（SQ 29 548; IC50 = 30 Nmol / L），显示出效果是受体的。检查下游信号传导途径，我们发现通过钙通道阻滞剂抑制这种相互作用（Diltiazem; IC50 =3μmol/ L和维拉帕米; IC50 =5μmol/ L），磷脂酶C（ PLC）抑制剂（U73122; IC50 =4μmol/ L），环氧酶抑制剂（吲哚美辛; IC50 =0.2μmol/ L）和丝裂原激活蛋白（MAP）激酶抑制剂（PD98059; IC50 =3μmol/ L）。特异性酪氨酸轻链激酶（TLCK）抑制剂，草霉素A，具有5μmol/升的异霉素A的效果也抑制。用5-HT和AA诱导的细胞内钙血小板的预处理，并且通过维拉帕米阻断了这种效果。结论：血小板聚集中5-HT和AA之间的协同作用涉及PLC / CA2 +，COX和MAP激酶途径的激活。

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