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在缺乏上皮的离体气道平滑肌制剂中,维拉帕米的作用减弱。

The effect of verapamil is reduced in isolated airway smooth muscle preparations lacking the epithelium.

作者信息

Raeburn D, Hay D W, Robinson V A, Farmer S G, Fleming W W, Fedan J S

出版信息

Life Sci. 1986 Mar 3;38(9):809-16. doi: 10.1016/0024-3205(86)90597-7.

DOI:10.1016/0024-3205(86)90597-7
PMID:3512945
Abstract

The effect of epithelium removal on the reactivity of rabbit airway smooth muscle to bronchoactive agents and on the effect of verapamil was studied in vitro using preparations from several levels within the respiratory tree, i.e., trachea, primary (10) and secondary (20) bronchus. Methacholine contracted tissues from all three levels of airway. Histamine contracted strips from 20 bronchus, had an inconsistent action in strips from 10 bronchus and was without effect in tracheal preparations. K+ contracted tissues from the trachea and 10 bronchus, and had a mixed action in 20 bronchial strips. Removal of the epithelial cell layer variably affected the reactivity of the smooth muscle to the three agents studied. In 20 bronchus, epithelium removal potentiated responses to histamine and methacholine. In 10 bronchus, only responses to methacholine were consistently augmented. In tracheal preparations epithelium removal did not alter the reactivity of the tissue to any agent examined. Verapamil (1 microM) attenuated responses to all agents and increased in its potency from tracheal through 10 to 20 bronchial preparations. Following epithelium removal, verapamil was substantially less effective in 20 bronchi, yet its effects were unchanged in the trachea. The results indicate that the epithelial cell layer modulates airway smooth muscle reactivity; this phenomenon is apparently widespread in mammals, the modulatory effect is more prominent in the smaller airways, and the magnitude of the effect of verapamil on airway smooth muscle is, in part, related to the presence of the epithelium.

摘要

利用呼吸树不同水平的组织标本,即气管、一级(10)和二级(20)支气管,在体外研究了去除上皮对兔气道平滑肌对支气管活性剂反应性的影响以及维拉帕米的作用。乙酰甲胆碱使来自气道所有三个水平的组织收缩。组胺使来自20级支气管的条带收缩,对来自10级支气管的条带作用不一致,对气管标本无作用。钾离子使气管和10级支气管的组织收缩,对20级支气管条带作用混合。去除上皮细胞层对平滑肌对所研究的三种药物的反应性有不同影响。在20级支气管中,去除上皮增强了对组胺和乙酰甲胆碱的反应。在10级支气管中,仅对乙酰甲胆碱的反应持续增强。在气管标本中,去除上皮并未改变组织对任何所检测药物的反应性。维拉帕米(1微摩尔)减弱了对所有药物的反应,其效力从气管到10级支气管再到20级支气管标本逐渐增强。去除上皮后,维拉帕米在20级支气管中的效果明显降低,但其在气管中的作用未改变。结果表明上皮细胞层调节气道平滑肌反应性;这种现象在哺乳动物中显然普遍存在,调节作用在较小气道中更突出,维拉帕米对气道平滑肌的作用大小部分与上皮的存在有关。

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引用本文的文献

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The effects of epithelium removal on the sensitivity of guinea-pig isolated trachealis to bronchodilator drugs.上皮去除对豚鼠离体气管对支气管扩张药物敏感性的影响。
Br J Pharmacol. 1986 Oct;89(2):407-14. doi: 10.1111/j.1476-5381.1986.tb10274.x.
2
Differential effects of epithelium removal on the responsiveness of guinea-pig tracheal smooth muscle to bronchoconstrictors.去除上皮对豚鼠气管平滑肌对支气管收缩剂反应性的不同影响。
Br J Pharmacol. 1987 Oct;92(2):381-8. doi: 10.1111/j.1476-5381.1987.tb11334.x.
3
The epithelium and the pharmacology of guinea-pig tracheal tone in vitro.
豚鼠气管体外张力的上皮组织与药理学
Br J Pharmacol. 1988 Apr;93(4):909-17. doi: 10.1111/j.1476-5381.1988.tb11479.x.
4
Effect of verapamil and sodium cromoglycate on leukotriene D4 induced bronchoconstriction in patients with asthma.维拉帕米和色甘酸钠对哮喘患者白三烯D4诱导的支气管收缩的作用。
Thorax. 1986 Oct;41(10):753-8. doi: 10.1136/thx.41.10.753.
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Epithelium derived relaxing factor: myth or reality?上皮衍生舒张因子:神话还是现实?
Thorax. 1988 Sep;43(9):665-8. doi: 10.1136/thx.43.9.665.
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Production of arachidonic and linoleic acid metabolites by guinea pig tracheal epithelial cells.豚鼠气管上皮细胞产生花生四烯酸和亚油酸代谢物。
Inflammation. 1990 Aug;14(4):401-8. doi: 10.1007/BF00914091.
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