Centre of Excellence for the Study of Inflammation, University of Ferrara, Italy.
Br J Pharmacol. 2009 Nov;158(6):1621-8. doi: 10.1111/j.1476-5381.2009.00438.x. Epub 2009 Oct 20.
The transient receptor potential ankyrin receptor 1 (TRPA1) is a cation channel, co-expressed with the pro-tussive transient receptor potential vanilloid type 1 (TRPV1) channel in primary sensory neurons. TRPA1 is activated by a series of irritant exogenous and endogenous alpha,beta-unsaturated aldehydes which seem to play a role in airway diseases. We investigated whether TRPA1 agonists provoke cough in guinea pigs and whether TRPA1 antagonists inhibit this response.
Animals were placed in a Perspex box, and cough sounds were recorded and counted by observers unaware of the treatment used.
Inhalation of two selective TRPA1 agonists, allyl isothiocyanate and cinnamaldehyde, dose-dependently caused cough in control guinea pigs, but not in those with airway sensory nerves desensitized by capsaicin. Coughs elicited by TRPA1 agonists were reduced by non-selective (camphor and gentamicin) and selective (HC-030031) TRPA1 antagonists, whereas they were unaffected by the TRPV1 antagonist, capsazepine. Acrolein and crotonaldehyde, two alpha,beta-unsaturated aldehydes recently identified as TRPA1 stimulants and contained in cigarette smoke, air pollution or produced endogenously by oxidative stress, caused a remarkable tussive effect, a response that was selectively inhibited by HC-030031. Part of the cough response induced by cigarette smoke inhalation was inhibited by HC-030031, suggesting the involvement of TRPA1.
A novel pro-tussive pathway involves the TRPA1 channel, expressed by capsaicin-sensitive airway sensory nerves and is activated by a series of exogenous (cigarette smoke) and endogenous irritants. These results suggest TRPA1 may be a novel target for anti-tussive medicines.
瞬时受体电位锚蛋白受体 1（TRPA1）是一种阳离子通道，与初级感觉神经元中的促吐性瞬时受体电位香草醛 1 型（TRPV1）通道共表达。TRPA1 被一系列刺激性外源性和内源性α，β-不饱和醛激活，这些醛似乎在气道疾病中发挥作用。我们研究了 TRPA1 激动剂是否会引起豚鼠咳嗽，以及 TRPA1 拮抗剂是否会抑制这种反应。
动物被放置在聚碳酸酯盒中，通过观察者记录和计数咳嗽声音，而观察者不知道所使用的处理方法。
两种选择性 TRPA1 激动剂丙烯基异硫氰酸酯和肉桂醛吸入可剂量依赖性地引起对照豚鼠咳嗽，但不能引起气道感觉神经被辣椒素敏化的豚鼠咳嗽。TRPA1 激动剂引起的咳嗽被非选择性（樟脑和庆大霉素）和选择性（HC-030031）TRPA1 拮抗剂减少，而 TRPV1 拮抗剂辣椒素则没有影响。丙烯醛和巴豆醛，两种最近被鉴定为 TRPA1 兴奋剂的α，β-不饱和醛，存在于香烟烟雾、空气污染或由氧化应激产生的内源性物质中，引起明显的咳嗽效应，这种反应被 HC-030031 选择性抑制。HC-030031 抑制部分香烟烟雾吸入引起的咳嗽反应，提示 TRPA1 的参与。
一种新的促吐途径涉及 TRPA1 通道，由辣椒素敏感的气道感觉神经表达，并被一系列外源性（香烟烟雾）和内源性刺激物激活。这些结果表明 TRPA1 可能是一种新型的镇咳药物靶点。
