Webber S E, Kitt A, Yurdakos E, Widdicombe J G
Department of Physiology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, U.K.
Pulm Pharmacol Ther. 1997 Jun;10(3):157-66. doi: 10.1006/pupt.1997.0089.
Both PAF (10 microM) and bradykinin (0.1-10 microM) increased lysozyme (from submucosal gland serous cells (+138 and +45% for PAF, 10 microM, and bradykinin, 1 microM, respectively) and albumin (mainly active epithelial transport; +387 and +108%) outputs into the ferret tracheal lumen in vitro and reduced the negativity of the potential difference (PD: -33 and -17%) across the trachea. Since PAF can cause bronchial smooth muscle hyperresponsiveness, we tested whether these effects were interactive, and if PAF would increase the actions of bradykinin. The bradykinin-induced lysozyme and albumin outputs were more than trebled and the PD change was enhanced by PAF, after the immediate secretory effects of the latter had returned to baseline. The secretory and PD responses to PAF were all prevented by the PAF-antagonist WEB 2086 and by a combination of the free-radical scavengers catalase and SOD, indicating that PAF may act on specific receptors to release free-radicals. Nedocromil sodium inhibited the increase in lysozyme and albumin outputs produced by PAF, but had no effect on the PD response. None of the tracheal responses to bradykinin was modified by WEB 2086, catalase and SOD, or nedocromil sodium. The secretory and PD hyperresponsiveness to bradykinin caused by PAF was prevented by WEB 2086 and by catalase and SOD. Nedocromil sodium greatly inhibited the lysozyme and albumin hyperresponsiveness but had no effect on the PD response. Thus PAF may release more than one type of radical which have differential effects on serous cells and albumin transport compared with PD; nedocromil sodium may act only against the radical causing the secretory effects.
血小板活化因子（PAF，10微摩尔）和缓激肽（0.1 - 10微摩尔）均可增加溶菌酶（来自黏膜下腺浆液细胞，PAF 10微摩尔和缓激肽1微摩尔时分别增加138%和45%）和白蛋白（主要是活性上皮转运；分别增加387%和108%）向雪貂气管腔的体外分泌量，并降低气管跨膜电位差（PD）的负值（分别降低33%和17%）。由于PAF可引起支气管平滑肌高反应性，我们测试了这些效应是否具有相互作用，以及PAF是否会增强缓激肽的作用。在PAF的即时分泌效应恢复到基线后，PAF使缓激肽诱导的溶菌酶和白蛋白分泌量增加了两倍多，且PD变化增强。PAF拮抗剂WEB 2086以及自由基清除剂过氧化氢酶和超氧化物歧化酶的组合均可阻止对PAF的分泌和PD反应，表明PAF可能作用于特定受体以释放自由基。奈多罗米钠抑制PAF引起的溶菌酶和白蛋白分泌量增加，但对PD反应无影响。WEB 2086、过氧化氢酶、超氧化物歧化酶或奈多罗米钠均未改变气管对缓激肽的反应。WEB 2086、过氧化氢酶和超氧化物歧化酶可阻止PAF引起的对缓激肽的分泌和PD高反应性。奈多罗米钠极大地抑制了溶菌酶和白蛋白高反应性，但对PD反应无影响。因此，PAF可能释放不止一种类型的自由基，与PD相比，这些自由基对浆液细胞和白蛋白转运具有不同的作用；奈多罗米钠可能仅作用于引起分泌效应的自由基。
