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首页> 外文期刊>The Open Drug Discovery Journal >The Rising Role of TRPA1 in Asthma
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The Rising Role of TRPA1 in Asthma

机译：TRPA1在哮喘中的上升作用

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Asthma is an inflammatory condition of the airways triggered by exposure to allergens and/or irritants. TRPA1is an irritant-sensing cation channel expressed in TRPV1-positive, capsaicin-sensitive chemosensory neurons thatinnervate various organs, including the airways. Various exogenous noxious chemicals have been described to activateTRPA1, including agents recognized to trigger and/or worsen asthma such as diisocyantes, cigarette smoke, acrolein,chlorine. During oxidative stress, a condition associated with asthma, various chemical species capable of activatingTRPA1 are generated in the lungs, including reactive oxygen species (ROS), reactive nitrogen species (RNS), and severalbyproducts of lipid peroxidation including nitrooleic acid and 4-hydroxynonenal. Recently, a potential role of TRPA1 inmediating allergen-induced asthmatic responses has been described in ovalbumin-sensitized mice, in which geneticdeletion of TRPA1 or pretreatment with a selective TRPA1 antagonist reduced leukocyte infiltration, decreased cytokineand mucus production and almost completely abolished airway hyperreactivity without affecting the immune responsedriven by the allergen. Moreover, two recent studies have provided strong pharmacological evidence that inhalation ofTRPA1 activators, like acrolein or cinnamaldehyde, elicits cough reflexes in guinea-pigs and human volunteers. Inconclusion, a compelling series of recent findings highlights the TRPA1 channel as a molecular target for a wide varietyof known exogenous and endogenous inflammatory and irritating chemical agents, and suggests that TRPA1 antagonistsmight be taken into consideration as a novel pharmacological treatment of asthma, chronic cough and possibly otherinflammatory conditions of the airways.
机译：哮喘是由于接触过敏原和/或刺激物而引起的气道炎症性疾病。 TRPA1是在TRPV1阳性，对辣椒素敏感的化学感应神经元中表达的刺激性阳离子通道，可刺激包括呼吸道在内的各种器官。已经描述了各种外源性有害化学物质来激活TRPA1，包括公认的引发和/或加剧哮喘的物质，例如二异氰酸酯，香烟烟雾，丙烯醛，氯。在氧化应激（一种与哮喘有关的疾病）期间，会在肺中生成各种能够激活TRPA1的化学物质，包括活性氧（ROS），活性氮（RNS）和脂质过氧化的几种副产物，包括亚硝酸和4-羟基壬烯醛。最近，在卵白蛋白致敏的小鼠中已经描述了TRPA1介导变应原诱发的哮喘反应的潜在作用，其中TRPA1的遗传缺失或选择性TRPA1拮抗剂的预处理减少了白细胞浸润，减少了细胞因子和粘液的产生，并且几乎完全消除了气道高反应性而不影响过敏原驱动的免疫反应。此外，最近的两项研究提供了强有力的药理学证据，表明吸入TRPA1激活剂（如丙烯醛或肉桂醛）会诱发豚鼠和人类志愿者的咳嗽反射。总而言之，一系列令人信服的最新发现突显出TRPA1通道是多种已知外源性和内源性炎症和刺激性化学制剂的分子靶标，并建议将TRPA1拮抗剂作为哮喘，慢性咳嗽和哮喘的新型药物治疗方法考虑在内。可能是气道的其他炎症状况。

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