Bai T R, Prasad F W
Department of Pharmacology, University of Auckland School of Medicine, New Zealand.
Can J Physiol Pharmacol. 1994 Mar;72(3):199-204. doi: 10.1139/y94-031.
The aim of this study was to test the hypothesis that the increase in maximal responses to histamine, acetylcholine, and cholinergic electrical field stimulation and decreased relaxant responses to isoprenaline reported in asthmatic tracheal smooth muscle result from the epithelial damage observed in asthma. The effect of mechanical removal of the epithelium on contractile and relaxant responses was examined in normal human postmortem tracheal smooth muscle strips. The epithelium was removed from alternate tracheal strips obtained from 25 subjects within 14 h of sudden death from nonrespiratory causes. In paired samples, contractile cholinergic and inhibitory nonadrenergic, noncholinergic (i-NANC) neural responses to electrical field stimulation and responses to exogenous histamine, potassium chloride, theophylline, and isoprenaline were unaffected by removal of the epithelium. However, the maximal isometric tension (Tmax) induced by methacholine increased by 70.1 +/- 19.8% (mean +/- SE, p < 0.005, n = 9), without alteration in EC50. These data suggest that disruption of the epithelium is unlikely to be the explanation of the abnormalities observed in trachea in fatal asthma. Explanations of the increase in maximal response to methacholine following removal of the epithelium include loss of an epithelium-derived relaxant factor released via an epithelial muscarinic receptor or loss of a specific permeability or metabolic barrier imposed by the epithelium for methacholine.
哮喘患者气管平滑肌中对组胺、乙酰胆碱和胆碱能电场刺激的最大反应增加以及对异丙肾上腺素的舒张反应降低是由哮喘中观察到的上皮损伤所致。在正常人体死后气管平滑肌条中，研究了机械去除上皮对收缩和舒张反应的影响。从25名因非呼吸原因突然死亡且死亡时间在14小时内的受试者获取的气管条中，交替去除上皮。在配对样本中，电场刺激引起的收缩性胆碱能和抑制性非肾上腺素能、非胆碱能（i-NANC）神经反应以及对外源性组胺、氯化钾、茶碱和异丙肾上腺素的反应不受上皮去除的影响。然而，乙酰甲胆碱诱导的最大等长张力（Tmax）增加了70.1±19.8%（平均值±标准误，p<0.005，n=9），而半数有效浓度（EC50）无变化。这些数据表明，上皮破坏不太可能是致命性哮喘患者气管中观察到的异常现象的原因。上皮去除后对乙酰甲胆碱最大反应增加的原因包括通过上皮毒蕈碱受体释放的上皮源性舒张因子丧失，或上皮对乙酰甲胆碱施加的特定通透性或代谢屏障丧失。
