Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants
Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants
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DOI：
10.1096/fj.11-188383
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发表时间：
2011-12-01
期刊：
影响因子：
4.8
通讯作者：
Morris, John B.
中科院分区：
文献类型：
--
作者：
Willis, Daniel N.;Liu, Boyi;Morris, John B.
薄荷脑，薄荷中的清凉剂，几乎被添加到所有的商业香烟中。Menglutamine刺激嗅觉，并与冷敏感感觉神经元中的瞬时受体电位melastatin 8（TRPM 8）离子通道和瞬时受体电位锚蛋白1（TRPA 1）（一种刺激感测通道）相互作用。香烟烟雾中的薄荷醇是否具有影响吸烟行为的药理作用一直存在争议。采用体积描记法，我们研究了薄荷醇对烟雾刺激物（丙烯醛、乙酸和环己酮）引起的小鼠呼吸感觉刺激反应的影响。薄荷脑的浓度（16 ppm）低于含薄荷脑香烟的烟雾，立即消除了对丙烯醛（TRPA 1的激动剂）的刺激反应，另一种TRPM 8激动剂桉叶醇（460 ppm）也是如此。TRPM 8拮抗剂AMTB可逆转Menglutamine的作用。薄荷脑的作用并不局限于丙烯醛，因为薄荷脑也能减弱对乙酸和环己酮（辣椒素受体TRPV 1的激动剂）的刺激反应。甲氨蝶呤在呼吸道中被有效吸收，达到足以激活感觉TRP通道的局部浓度。这些实验表明，薄荷醇和桉树脑，通过激活TRPM 8，作为有效的反刺激剂对广谱的烟雾成分。通过抑制呼吸道刺激，薄荷醇可以促进烟雾吸入，促进尼古丁成瘾和吸烟相关的疾病。威利斯，D. N.，Liu，B.，哈M一、Jordt，S. E、Morris，J. B.薄荷脑减弱对多种香烟烟雾刺激物的呼吸道刺激反应。FASEB J.25，4434-4444（2011）。www.fasebj.org
Menthol, the cooling agent in peppermint, is added to almost all commercially available cigarettes. Menthol stimulates olfactory sensations, and interacts with transient receptor potential melastatin 8 (TRPM8) ion channels in cold-sensitive sensory neurons, and transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing channel. It is highly controversial whether menthol in cigarette smoke exerts pharmacological actions affecting smoking behavior. Using plethysmography, we investigated the effects of menthol on the respiratory sensory irritation response in mice elicited by smoke irritants (acrolein, acetic acid, and cyclohexanone). Menthol, at a concentration (16 ppm) lower than in smoke of mentholated cigarettes, immediately abolished the irritation response to acrolein, an agonist of TRPA1, as did eucalyptol (460 ppm), another TRPM8 agonist. Menthol's effects were reversed by a TRPM8 antagonist, AMTB. Menthol's effects were not specific to acrolein, as menthol also attenuated irritation responses to acetic acid, and cyclohexanone, an agonist of the capsaicin receptor, TRPV1. Menthol was efficiently absorbed in the respiratory tract, reaching local concentrations sufficient for activation of sensory TRP channels. These experiments demonstrate that menthol and eucalyptol, through activation of TRPM8, act as potent counterirritants against a broad spectrum of smoke constituents. Through suppression of respiratory irritation, menthol may facilitate smoke inhalation and promote nicotine addiction and smoking-related morbidities.-Willis, D. N., Liu, B., Ha, M. A., Jordt, S.-E., Morris, J. B. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. FASEB J. 25, 4434-4444 (2011). www.fasebj.org