Sensory detection and responses to toxic gases: mechanisms, health effects, and countermeasures.
Sensory detection and responses to toxic gases: mechanisms, health effects, and countermeasures.
复制标题
DOI：
10.1513/pats.201001-004sm
复制
发表时间：
2010-07-01
期刊：
影响因子：
--
通讯作者：
Jordt, Sven-Eric
中科院分区：
文献类型：
--
作者：
Bessac, Bret F;Jordt, Sven-Eric
吸入反应性气体和蒸汽可导致气道和肺的严重损伤，损害呼吸系统的功能。暴露于氧化性、亲电性、酸性或碱性气体经常发生在职业和周围环境中。氯气、光气和氯化苦等腐蚀性气体和蒸汽被用作战争剂和恐怖主义行为。化学气道暴露通过嗅觉、味觉和伤害性感觉系统检测，这些系统启动保护性生理和行为反应。本文综述了气道伤害感受神经元在化学感受中的作用，并讨论了最近发现的反应性化学物质的神经元受体。使用生理学、成像和遗传学方法，感觉神经元中的瞬时受体电位（TRP）离子通道被证明对广泛的有害化学刺激作出反应，引发疼痛、呼吸抑制、咳嗽、腺体分泌物和其他保护性反应。TRPA1是一种在化学感受C纤维中表达的TRP离子通道，几乎所有的氧化和亲电子化学物质都能激活它，包括氯、丙烯醛、催泪瓦斯和异氰酸甲酯，后者是博帕尔灾难中释放的剧毒化学物质。化学物质可能通过共价蛋白修饰激活TRPA1。使用TRPA1拮抗剂或TRPA1缺陷小鼠的动物研究证实了TRPA1在体内化学诱导的呼吸反射、疼痛和炎症中的作用。新的研究表明，感觉神经元不仅仅是化学暴露的被动传感器。感觉通道如TRPA1对于维持哮喘的气道炎症是必不可少的，并且可能有助于高水平化学暴露后气道损伤的进展。
The inhalation of reactive gases and vapors can lead to severe damage of the airways and lung, compromising the function of the respiratory system. Exposures to oxidizing, electrophilic, acidic, or basic gases frequently occur in occupational and ambient environments. Corrosive gases and vapors such as chlorine, phosgene, and chloropicrin were used as warfare agents and in terrorist acts. Chemical airway exposures are detected by the olfactory, gustatory, and nociceptive sensory systems that initiate protective physiological and behavioral responses. This review focuses on the role of airway nociceptive sensory neurons in chemical sensing and discusses the recent discovery of neuronal receptors for reactive chemicals. Using physiological, imaging, and genetic approaches, Transient Receptor Potential (TRP) ion channels in sensory neurons were shown to respond to a wide range of noxious chemical stimuli, initiating pain, respiratory depression, cough, glandular secretions, and other protective responses. TRPA1, a TRP ion channel expressed in chemosensory C-fibers, is activated by almost all oxidizing and electrophilic chemicals, including chlorine, acrolein, tear gas agents, and methyl isocyanate, the highly noxious chemical released in the Bhopal disaster. Chemicals likely activate TRPA1 through covalent protein modification. Animal studies using TRPA1 antagonists or TRPA1-deficient mice confirmed the role of TRPA1 in chemically induced respiratory reflexes, pain, and inflammation in vivo. New research shows that sensory neurons are not merely passive sensors of chemical exposures. Sensory channels such as TRPA1 are essential for maintenance of airway inflammation in asthma and may contribute to the progression of airway injury following high-level chemical exposures.