Irritant-induced chronic cough: Irritant-induced TRPpathy
Irritant-induced chronic cough: Irritant-induced TRPpathy
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DOI：
10.1007/s00408-007-9068-0
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发表时间：
2008-01-01
期刊：
影响因子：
5
通讯作者：
Brooks, Stuart M.
中科院分区：
文献类型：
--
作者：
Brooks, Stuart M.
本文扩展了作者在2007年6月8-9日在纽约市举行的第一届美国咳嗽会议上的演讲。包括科学文献检索的结果和个人研究成果的应用。提出了一个新的假说，将刺激性咳嗽解释为位于肺可兴奋细胞的瞬时受体电位香草酸1（TRPV 1）阳离子通道功能障碍。TRPV 1阳离子通道通过升高细胞内Ca ~（2+）和Na ~+浓度以及使含有C纤维的感觉神经细胞去极化来调节细胞跨膜电压。讨论集中在“辣椒素受体”（TRPV 1）和另一个重要的离子通道TRPA 1上。作者回顾了已发表的科学研究结果，以支持他的论点，即由TRPV 1离子通道引发的神经事件导致了一系列变化，这些变化进展到咳嗽终点。在反复或严重刺激物诱导的气道上皮损伤（例如，RADS）是通过持续的TRPV 1通道激活（例如，TRPV 1病），伴随炎症介质、速激肽的积聚和神经营养因子的释放，导致持续性咳嗽和气道炎症。该假说的意义在于，如果得到证实，它可能为慢性咳嗽的治疗提供新的治疗方法。
This article expands the author's presentation at the First American Cough Conference in New York City, June 8-9, 2007. The results of a scientific literature search and application of personal research findings are included. A new hypothesis to explain irritant-induced cough as a being a dysfunction of the transient receptor potential vanilloid 1 (TRPV1) cation channels located in pulmonary excitable cells is presented. The TRPV1 cation channels reaulate cellular transmembrane voltage by raising intracellular Ca2+ and Na+ concentrations and depolarizing sensory nerve cells containing C-fibers. The discussion centers on the "capsaicin receptor" (TRPV1) and another important ion channel, TRPA1. The author reviews results of published scientific investigations to support his contention that neural events, initiated by TRPV1 ion channels, lead to a cascade of alterations that progress to a cough endpoint. A potential mechanism to explain chronic cough in conditions where there is repeated or severe irritant-induced airway epithelial injury (e.g., RADS) is through persistent TRPV1 channel activation (e.g., TRPV1pathy) with accumulation of inflammatory mediators, tachykinins, and the release of neurotrophins leading to persistent cough and airway inflammation. The significance of the hypothesis is that, if proven, it may provide new therapeutic approaches for the treatment of chronic cough.