The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol
The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol
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DOI：
10.1152/japplphysiol.01144.2012
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发表时间：
2013-07-01
影响因子：
3.3
通讯作者：
Canning, B. J.
中科院分区：
文献类型：
--
作者：
Plevkova, J.;Kollarik, M.;Canning, B. J.
冷敏感阳离子通道TRPM 8是薄荷醇的目标，薄荷醇通常用作止咳剂以及烟草和食品的添加剂。鉴于寒冷的温度和薄荷醇通过TRPM 8的门控激活神经元，目前还不清楚薄荷醇如何积极抑制咳嗽。在这项研究中，我们描述了（-）-薄荷醇在清醒和麻醉豚鼠的镇咳作用。在麻醉的豚鼠中，仅当薄荷醇选择性地以蒸汽形式给药于上呼吸道时，才能抑制局部应用于气管粘膜的柠檬酸诱发的咳嗽。在应用柠檬酸之前和期间，将孟诺明局部应用于气管粘膜，或以蒸汽或气雾剂形式持续给予下呼吸道，对咳嗽没有影响。上呼吸道薄荷醇治疗的这些作用通过递送到上呼吸道的冷空气来模拟，但不通过（+）-薄荷醇（薄荷醇的非活性异构体）或通过直接施用到气管的TRPM 8/TRPA 1激动剂icilin来模拟。随后的分子分析证实了TRPM 8在鼻三叉神经传入神经元的一个子集中的表达，这些神经元不同时表达TRPA 1或TRPV 1。我们的结论是，薄荷醇抑制咳嗽诱发下呼吸道主要是通过反射发起的鼻子。
The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (-)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose.