Del Monte M, Subissi A
Department of Pharmacology, Laboratori Guidotti SpA, Pisa, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Oct;338(4):417-21. doi: 10.1007/BF00172120.
The identification of the mediators possibly involved in platelet-activating factor (PAF)-induced contraction of guinea-pig lung parenchymal strips (GPLP) was attempted by means of antagonists and inhibitors. Histamine, serotonin, acetylcholine (ACh) or other transmitters released from the nerve terminals are not likely to play a role in this response, since specific antagonists and tetrodotoxin did not affect the contraction. PAF antagonists (brotizolam and WEB 2086) produced a concentration-dependent inhibition of the contraction. Inhibitors of TXA2 synthesis (dazoxiben) and of 5-lipoxygenase (nordihydroguaiaretic acid and AA 861) and antagonists of TXA2 (ICI 159995) and peptidoleukotrienes (L 649923 and LY 171883, but not FPL 55712) produced a significant inhibition of the PAF-induced response at concentrations which did not reduce the ACh-induced response. These results suggest that arachidonate metabolites, both of the cyclo-oxygenase and of the lipoxygenase pathway, are determinants of the PAF-induced contraction of GPLP.
通过使用拮抗剂和抑制剂，尝试确定可能参与血小板活化因子（PAF）诱导的豚鼠肺实质条（GPLP）收缩的介质。组胺、5-羟色胺、乙酰胆碱（ACh）或从神经末梢释放的其他递质不太可能在这种反应中起作用，因为特异性拮抗剂和河豚毒素并不影响收缩。PAF拮抗剂（溴替唑仑和WEB 2086）对收缩产生浓度依赖性抑制。血栓素A2（TXA2）合成抑制剂（达唑氧苯）、5-脂氧合酶抑制剂（去甲二氢愈创木酸和AA 861）以及TXA2拮抗剂（ICI 159995）和肽白三烯拮抗剂（L 649923和LY 171883，但不包括FPL 55712）在不降低ACh诱导反应的浓度下，对PAF诱导的反应产生显著抑制。这些结果表明，环氧化酶途径和脂氧合酶途径的花生四烯酸代谢产物是PAF诱导的GPLP收缩的决定因素。
