Holroyde M C
Br J Pharmacol. 1986 Mar;87(3):501-7. doi: 10.1111/j.1476-5381.1986.tb10192.x.
This study was designed to investigate the possibility that tracheal epithelium generates a relaxant factor analogous to the endothelial-derived relaxant factor (EDRF) of vascular tissue. The absence of such a factor following epithelial damage in diseases such as asthma might help to explain the airway hyperreactivity characteristic of such diseases. Removal of epithelium by rubbing enhanced the sensitivity of guinea-pig isolated tracheal chains to 5-hydroxytryptamine, histamine, acetylcholine, adenosine, isoprenaline and also minimally to KCl. Responses to LaCl3 and electrical field stimulation were not affected. Low concentrations of adenosine produced contractions only in tissues denuded of epithelium. In the presence of indomethacin 1.4 microM or dithiothreitol (DTT) 1 microM, dose-response curves to histamine were moved to the left in both control and rubbed tissues, and the maximum response was increased. The difference in sensitivity between tissues with and without epithelium was not affected by indomethacin, but was slightly reduced by DTT. Phenidone (0.1 mM) also increased the maximum responses, but increased the sensitivity only of the tissues with intact epithelium, to the same level as that seen in the tissues denuded of epithelium. Superfusion cascade studies provided no evidence for the generation of a relaxant factor from tracheal epithelium. It is suggested that the supersensitivity produced by removal of the epithelium is not due to the removal of a relaxant factor, but rather to the removal of a permeability barrier, allowing a greater concentration of agonist at the level of the underlying smooth muscle.
本研究旨在探讨气管上皮是否能产生一种类似于血管组织中内皮源性舒张因子（EDRF）的舒张因子。在哮喘等疾病中，上皮损伤后缺乏这种因子可能有助于解释此类疾病特有的气道高反应性。通过摩擦去除上皮可增强豚鼠离体气管链对5-羟色胺、组胺、乙酰胆碱、腺苷、异丙肾上腺素的敏感性，对氯化钾的敏感性也略有增强。对氯化镧和电场刺激的反应不受影响。低浓度的腺苷仅在去上皮组织中引起收缩。在存在1.4微摩尔吲哚美辛或1微摩尔二硫苏糖醇（DTT）的情况下，对照组织和摩擦组织中组胺的剂量-反应曲线均向左移动，最大反应增强。有无上皮组织之间的敏感性差异不受吲哚美辛影响，但DTT使其略有降低。非那吡啶（0.1毫摩尔）也增加了最大反应，但仅增加了完整上皮组织的敏感性，使其与去上皮组织中的敏感性相同。灌流串联研究未提供气管上皮产生舒张因子的证据。提示去除上皮产生的超敏反应不是由于去除了舒张因子，而是由于去除了通透性屏障，使激动剂在下层平滑肌水平达到更高浓度。
