Role of the epithelium in airway smooth muscle responses to relaxant agonists.

Role of the epithelium in airway smooth muscle responses to relaxant agonists.
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上皮在气道平滑肌对松弛激动剂的反应中的作用。

DOI:
10.1152/jappl.1991.71.4.1434
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发表时间:
1991
期刊:
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子:
--
通讯作者:
Hirshman,C
Hirshman,C
中科院分区:
--
文献类型:
--
作者:
Yang,JN;Mitzner,W;Hirshman,C

文献摘要

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我们研究了豚鼠气管上皮在调节气管平滑肌对松弛剂沙丁胺醇、硝普钠和茶碱的反应中的作用。我们使用了一种体外制剂,可以分离气管管腔(内部)和浆膜(外部)表面的液体,并将支气管扩张剂施用于经碳水化合物收缩的气管的任一表面。这三种药物都产生剂量依赖性松弛。然而,沙丁胺醇和硝普塞的效力较弱(产生半最大作用的浓度分别增加了100倍和32倍),当上皮完整时给予上皮,与剥去上皮或与浆膜给药相比,上皮完整。这些差异在茶碱中没有观察到,其中平滑肌反应与刺激的一侧或上皮的存在与否无关。直接测量在有无上皮存在的情况下,茶碱在气管壁上的扩散表明,在固定管腔浓度的茶碱孵育5小时后,在上皮完好的情况下,只有1.7%的茶碱在气管壁上扩散。当上皮被剥去时,这一比例增加到仅约3.3%。这些结果表明,上皮对亲脂剂是一个相对较弱的屏障,但对亲水物质具有主要的扩散屏障作用。
We studied the role of the guinea pig tracheal epithelium in modulating tracheal smooth muscle responses to the relaxant agonists albuterol, sodium nitroprusside, and theophylline. We used an in vitro preparation that allowed separation of the fluids bathing the luminal (internal) and serosal (external) surfaces of the trachea, and bronchodilators were administered to either surface of carbachol-contracted tracheae. All three drugs produced dose-dependent relaxation. However, albuterol and nitroprusside were less potent (concentration that produced half-maximal effect increased by 100- and 32-fold, respectively) when given to the epithelial side with the epithelium intact compared with the epithelium denuded or compared with serosal administration with the epithelium intact. These differences were not observed for theophylline, where smooth muscle responses were independent of either the side of stimulation or of the presence or absence of the epithelium. Direct measurements of the diffusion of theophylline across the tracheal wall in the presence or absence of epithelium showed that after 5 h of incubation with a fixed luminal concentration of theophylline, only 1.7% had diffused across the tracheal wall with the epithelium intact. This increased to only approximately 3.3% when the epithelium was denuded. These results suggest that the epithelial is a relatively weak barrier for lipophilic agents but has a major role as a diffusion barrier to hydrophilic substances.