Mechanism of expression of the ionic currents specific to chronic inflammatory airways.

1.比较了SO2气体暴露5~7wk后，对照组和支气管炎模型兔气管上皮细胞中CFTR(囊性纤维化跨膜电导调节因子)-mRNA的表达。Northern印迹分析表明，在SO2暴露的兔上皮细胞中CFTR-mRNA有较强的表达，而在正常对照兔中则没有表达。综合电生理和免疫组织化学研究的结果，我们得出结论：支气管炎上皮中的信号电流是由支气管炎上皮中上调的CFTRC1^通道介导的。我们研究了红霉素(EM)及其衍生物对猫气管气道腺离子电流的急性影响。治疗浓度的EM或克拉霉素(CAM)以竞争性方式减弱乙酰胆碱(ACh)诱发的全细胞电流。EM和CAM使对照组最大内向电流分别减少到54和83.96，外向K~+电流分别减少到55和84.96，而去甲肾上腺素、咖啡因和离子霉素对去甲肾上腺素、去甲肾上腺素、咖啡因和离子霉素的反应不受大环内酯类化合物EM、CAM或EM.K~+通道的合成衍生物EMS-23的影响。尽管治疗浓度的大环内酯类药物对基线电流没有影响，但高浓度的大环内酯类药物单独引起模拟ACh反应的电流，这种电流可被阿托品完全消除。我们的结论是，大环内酯类化合物作为胆碱能受体的部分激动剂，导致药物药理剂量下的C_1~-分泌减少，这可能对病理性呼吸道肥大和/或胆碱敏感的粘膜下腺有明显的疗效。

1. We have compared the expression of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)-mRNA in tracheal epithelium in control rabbits and bronchitis model rabbits which were exposed to SO2-gas for 5-7 wk. The Northern blot analysis revealed a strong expression of CFTR-mRNA in SO_2-exposedepithelium but not in control healthy rabbits. Taken together with the results obtained in elctrophysiological and immunohistochemical studies, we concluded that the signature current identified in bronchitic epithelium was mediated by upregulated CFTR C1^- channel in bronchitic epithelium.2. We investigated the acute effects of erythromycin (EM) and its derivatives on ionic currents in airway glands from feline tracheas. Therapeutic concentrations of EM or clarithromycin (CAM) attenuated the whole cell currents evoked by acetylcholine (ACh) in a competitive manner. The maximally stimulated inward C1^-currents were reduced to 54 and 83 96, and the outward K^+- currents to 55 and84 96 of controls by EM and CAM, respectively, whereas the responses induced by phenylephrine, norepinephrine, caffeine or ionomycin were unaffected by EM,CAM or EMS 23, a synthetic derivative of EM.K^+ channels in excised outside-out patches were not influenced by macrolides. Although therapeutic concentrations of macrolides showed no effect on the baseline currents, high concentrations of macrolides alone evoked currents mimicking the ACh-response, which were abolished completely by atropine. We concluded that macrolides act as a partial agonist on cholinergic receptors, resulting in a reduction of C1^- secretion atpharmacological doses of the agents, which may exhibit a pronounced effectiveness on hypertrophied and/or cholinergically-sensitized submucosalglands in pathological airways.