Frossard N, Rhoden K J, Barnes P J
Department of Thoracic Medicine, Brompton Hospital, London, United Kingdom.
J Pharmacol Exp Ther. 1989 Jan;248(1):292-8.
We have studied the effect of epithelium removal on the contractile responses to exogenous tachykinins and to endogenous tachykinins released by capsaicin in guinea pig trachea. We also studied the effects of inhibition of endopeptidase (by phosphoramidon, 10 microM, and thiorphan, 100 microM), and of inhibition of cyclooxygenase (by indomethacin, 5 microM) on these responses. The order of potency of exogenous tachykinins was neurokinin A (NKA) greater than neurokinin B (NKB) greater than substance P (SP). Epithelium removal enhanced the sensitivity and magnitude of the contractile response to SP, and to a lesser extent NKA and NKB. Capsaicin induced only a weak contractile response in guinea pig trachea. Phosphoramidon and thiorphan increased the sensitivity to SP, but had no effect on acetylcholine responses. The leftwardshift due to epithelium removal was reduced, but not abolished, by phosphoramidon and thiorphan. NKA- and NKB-induced contractions were also enhanced significantly by phosphoramidon. The effect of epithelium removal was abolished for NKA, but not for NKB. Phosphoramidon also increased significantly the contraction to capsaicin in the presence of epithelium, without altering the response obtained in the absence of epithelium. Indomethacin potentiated the sensitivity and maximal contractile response to all the tachykinins with the greatest effect on SP responses, and to capsaicin. The combination of indomethacin with phosphoramidon or thiorphan abolished the effect of epithelium removal for all the tachykinins. We conclude that the effects of exogenous and endogenous tachykinins are enhanced by removal of epithelium and by inhibition of metalloendopeptidase and cyclooxygenase, suggesting that tachykinins may be degraded by epithelial enzymes, and may release relaxant prostanoids in airways.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了去除上皮对豚鼠气管中外源性速激肽以及辣椒素释放的内源性速激肽收缩反应的影响。我们还研究了内肽酶抑制剂（10微摩尔磷酰胺脒和100微摩尔硫磷酰胺）以及环氧合酶抑制剂（5微摩尔吲哚美辛）对这些反应的影响。外源性速激肽的效力顺序为神经激肽A（NKA）＞神经激肽B（NKB）＞P物质（SP）。去除上皮增强了对SP收缩反应的敏感性和幅度，对NKA和NKB的影响较小。辣椒素在豚鼠气管中仅诱导出微弱的收缩反应。磷酰胺脒和硫磷酰胺增加了对SP的敏感性，但对乙酰胆碱反应无影响。磷酰胺脒和硫磷酰胺可减少因去除上皮导致的左移，但未完全消除。磷酰胺脒也显著增强了NKA和NKB诱导的收缩。去除上皮对NKA的影响被消除，但对NKB未消除。在有上皮存在时，磷酰胺脒也显著增加了对辣椒素的收缩反应，而不改变无上皮时的反应。吲哚美辛增强了对所有速激肽的敏感性和最大收缩反应，对SP反应和辣椒素的影响最大。吲哚美辛与磷酰胺脒或硫磷酰胺联合使用可消除去除上皮对所有速激肽的影响。我们得出结论，去除上皮以及抑制金属内肽酶和环氧合酶可增强外源性和内源性速激肽的作用，提示速激肽可能被上皮酶降解，并可能在气道中释放舒张性前列腺素。（摘要截断于250字）
