Epithelium removal alters responsiveness of guinea pig trachea to substance P.
Epithelium removal alters responsiveness of guinea pig trachea to substance P.
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上皮去除改变了豚鼠气管对 P 物质的反应性。
DOI：
10.1152/jappl.1989.66.1.232
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Sheppard,D
中科院分区：
文献类型：
--
作者：
Fine,JM;Gordon,T;Sheppard,D
已证明从哺乳动物气管去除上皮可以增强对多种收缩剂和松弛剂的反应性。据报道，最显着的变化之一是豚鼠气管组织被剥去上皮并用 P 物质处理。我们研究了这种反应性的变化是否是因为 1) 去除了上皮相关酶、中性肽链内切酶，该酶可降解 P 物质；2) 上皮来源的非环氧合酶松弛因子的损失。使用肌肉浴制剂，我们在经过吲哚美辛处理的组织（有或没有完整上皮）以及有或没有用中性肽链内切酶抑制剂磷酰胺预处理的组织上绘制了 P 物质和乙酰胆碱的浓度-反应曲线。上皮去除增强了平均激动剂浓度，经计算可引起最大收缩反应的 30%，P 物质增强了 148 倍，乙酰胆碱增强了 7 倍。磷酰胺增强了上皮完整组织和裸露组织对 P 物质的收缩反应，但不增强对乙酰胆碱的收缩反应（P 小于 0.05）。然而，在完整组织中，磷酰胺的增强程度要大得多。因此，通过磷酰胺处理，完整组织和裸露组织之间对 P 物质的反应性差异从 148 倍减少到 18 倍。磷酰胺的这种作用表明，上皮剥脱的气道组织对 P 物质的高反应性很大程度上是由于中性内肽酶的去除。因为所有组织都用吲哚美辛处理，所以上皮去除引起的 P 物质和乙酰胆碱反应性的左移进一步表明，除中性内肽酶之外的上皮衍生的非环氧合酶因子也调节对 P 物质和乙酰胆碱的收缩反应。
Removal of epithelium from mammalian tracheae has been shown to enhance responsiveness to a variety of contractile and relaxant agents. One of the most dramatic shifts reported has been for guinea pig tracheal tissue denuded of epithelium and treated with substance P. We investigated whether this shift in responsiveness was because of 1) removal of an epithelium-associated enzyme, neutral endopeptidase, which degrades substance P and 2) loss of an epithelium-derived noncyclooxygenase relaxant factor. Using a muscle bath preparation we performed concentration-response curves with substance P and acetylcholine on indomethacin-treated tissues with and without intact epithelium and with and without pretreatment with the neutral endopeptidase inhibitor, phosphoramidon. Epithelium removal potentiated the mean agonist concentration calculated to causes 30% of the maximal contractile response by 148-fold for substance P and by 7-fold for acetylcholine. Phosphoramidon potentiated the contractile response to substance P, but not to acetylcholine, by both the epithelium-intact and denuded tissues (P less than 0.05). However, the degree of enhancement by phosphoramidon was much greater in the intact tissues. With phosphoramidon treatment, therefore, the difference in responsiveness to substance P between the intact and denuded tissues was reduced from 148-fold to 18-fold. This effect of phosphoramidon suggests that the hyperresponsiveness to substance P of epithelium-denuded airway tissue is largely because of removal of neutral endopeptidase. Because all tissues were treated with indomethacin, the leftward shifts in substance P and in acetylcholine responsiveness induced by epithelium removal further suggest that an epithelium-derived noncyclooxygenase factor other than neutral endopeptidase also modulates the contractile response to substance P and to acetylcholine.