血小板活化因子和肾上腺素对人血小板凝集的钙依赖性协同作用

• 来源期刊: 中国药理学报（英文版）
• 学科: 医学
• 关键词: 血小板活化因子 肾上腺素 血小板聚集 地尔硫 维拉帕米 育亨宾 WEB-2086
• 年，卷（期）: 2003,（1）
• 所属期刊栏目: 研究原著
• 页码范围: 31-36
• 页数: 6页
• 分类号: R692
• 语种: 英文

摘要

AIM: To investigate the mechanism (s) involved in the synergistic interaction of platelet activating factor (PAF) and epinephrine. METHODS: Blood was obtained from healthy human subjects reported to be free of medications for at least two weeks before sampling. Aggregation was monitored at 37 ℃ using Dual-channel Lumi-aggregometer.The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time.RESULTS: Platelet aggregation mediated by subthreshold concentrations of PAF (5-8 nmol/L) plus epinephrine (0.5-2 μmol/L) was inhibited by α2-receptor blocker, yohimbine, and PAF receptor antagonist WEB 2086. This synergism was inhibited by calcium channel blockers, verapamil and diltiazem. In addition, platelet aggregation by co-addition of PAF and epinephrine was also inhibited by very low concentrations of phospholipase C (PLC)inhibitor (U73122; IC50=0.2 μmol/L), the MAP kinase inhibitor, PD 98059 (IC50=3 μmol/L), and cyclooxygenase (COX-1) inhibitors including indomethacin (IC50=0.25 μmol/L), flurbiprofen (IC50=0.7 μmol/L), and piroxicam (IC50=7 μmol/L). However, COX-2 inhibitors, nimesulide (IC50=26 μmol/L), NS-398 (IC50=7 μmol/L), and etodolac (IC50=15 μmol/L) were also effective in inhibiting the aggregation. The inhibitors of protein kinase C (chelerythrine)and tyrosine kinase (genistien), and phosphatidylinositol 3-kinase inhibitor (wortmannin) had no significant effect on platelet aggregation induced by PAF and epinephrine. CONCLUSION: The synergistic effect of PAF and epinephrine on human platelet aggregation is receptor-mediated and involves the activation of PLC/Ca2+, COX and MAP kinase signalling pathways.