Daffonchio L, Hernandez A, Martinotti E, Omini C
Institute of Pharmacological Sciences, University of Milan, Italy.
Pharmacol Res. 1990 Jan-Feb;22(1):49-58. doi: 10.1016/1043-6618(90)90743-w.
In guinea-pig isolated tracheae precontracted with pilocarpine (2 x 10(-5)M) mechanical removal of the epithelium did not significantly modify the degree of relaxation induced by three different adrenergic agonists: epinephrine (adrenaline), isoproterenol (isoprenaline) and salbutamol. The failure of epithelium removal to modify isoproterenol relaxant activity was observed in both spontaneous tone and pilocarpine precontracted tracheae. In tracheae obtained from actively sensitized (ovalbumin) guinea-pigs, log-concentration response curves of epinephrine and salbutamol were unchanged by epithelium damage, whereas that of isoproterenol was slightly shifted to the left. In ovalbumin sensitized tracheae exposed to the antigen (ovalbumin, 50 micrograms/ml) epithelium removal enhanced the relaxant activity of the three adrenergic agonists used. Beta-adrenoceptor desensitization (isoproterenol, 10(-6)M for 20 min twice) carried out in ovalbumin actively sensitized tracheae with or without epithelium, shifted the log-concentration response curves of isoproterenol to a similar rightward position. The present data suggest that the airway epithelium plays a minor role in the regulation of guinea-pig tracheal sensitivity to beta-adrenoceptor agonists, which is evident only in a classical model of experimental asthma.
在预先用毛果芸香碱（2×10⁻⁵M）预收缩的豚鼠离体气管中，机械去除上皮并未显著改变三种不同肾上腺素能激动剂（肾上腺素、异丙肾上腺素和沙丁胺醇）诱导的舒张程度。在自发张力和毛果芸香碱预收缩的气管中均观察到去除上皮未能改变异丙肾上腺素的舒张活性。在从主动致敏（卵清蛋白）豚鼠获得的气管中，肾上腺素和沙丁胺醇的对数浓度反应曲线不受上皮损伤的影响，而异丙肾上腺素的曲线略有左移。在暴露于抗原（卵清蛋白，50微克/毫升）的卵清蛋白致敏气管中，去除上皮增强了所使用的三种肾上腺素能激动剂的舒张活性。在有或无上皮的卵清蛋白主动致敏气管中进行β-肾上腺素能受体脱敏（异丙肾上腺素，10⁻⁶M，两次，每次20分钟），可使异丙肾上腺素的对数浓度反应曲线右移至相似位置。目前的数据表明，气道上皮在调节豚鼠气管对β-肾上腺素能激动剂的敏感性中起次要作用，这仅在经典的实验性哮喘模型中明显。
