权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Counter-Irritation by Menthol: Molecular Targets and Role in Airway Disease

薄荷醇抗刺激：分子靶标及其在气道疾病中的作用

基本信息

批准号：
8209236
负责人：
SVEN-ERIC JORDT
金额：
$ 40.42万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8209236
关键词：
Acrolein Acute Address Affect Afferent Neurons Analgesics Asthma Behavioral Biochemical Biological Factors Breathing C Fiber Chemicals Chronic Chronic Obstructive Airway Disease Cigarette Cigarette smoke-induced emphysema Cotinine Coughing Disease Exposure to Food Gene Family Goals Government Hypertension Hypesthesia Image Individual Inflammation Inflammatory Inhalation Exposure Ion Channel Irritants Lung Inflammation Lung diseases Malignant neoplasm of lung Mediating Mentha piperita Menthol Minority Modeling Molecular Molecular Target Mouse Strains Mus Nerve Fibers Neurons Neuropeptides Nicotine Nicotine Dependence Nociception Outcome Pain Pharmaceutical Preparations Physiological Pneumonia Population Process Protein Isoforms Publishing Receptor Signaling Research Respiratory System Role Sensory Serum Smoke Smoker Smoking Symptoms System TRPA1 Channel Terpenes Testing Therapeutic Time Tobacco Tobacco smoke Work afferent nerve base cigarette smoking insight irritation mouse model receptor research study respiratory respiratory reflex response smoke inhalation vapor

项目摘要

Project Summary Menthol, the cooling terpene derived from peppermint, is widely used for the treatment of cough, respiratory irritation and pain. As a cigarette additive menthol is especially popular with beginning smokers and in minority populations disproportionally affected by COPD, lung cancer and hypertension. It is currently unclear whether menthol contributes to these disease conditions through inhibition of the respiratory irritation response mediated by chemosensory neurons. Recently, two sensory menthol receptors were identified: TRPM8, the cold/menthol receptor, and TRPA1, a reactive irritant receptor. TRPA1 is activated by acrolein and other irritants contained in tobacco smoke. Our preliminary studies show that inhalation of menthol potently inhibits the respiratory irritation response to acrolein vapor in mice. Mice inhaling smoke from mentholated cigarettes showed higher serum levels of the nicotine metabolite, cotinine, than mice exposed to non-mentholated smoke, suggesting increased exposure to nicotine. In electrophysiological and fluorescent imaging experiments we show that menthol inhibits acrolein-activated TRPA1 channels. We hypothesize that: 1.) Menthol acts as a counterirritant, blocking sensory neuronal responses to inhaled noxious chemicals through interaction with the menthol receptors TRPA1 or TRPM8, and 2) As a tobacco additive, menthol facilitates smoke inhalation through inhibition of neuronal irritant receptor signalling, thereby accelerating nicotine dependence and lung disease. The studies proposed in this application will use physiological, biochemical, molecular and behavioral approaches to: Aim 1.) Define the roles of TRPA1 and TRPM8 in menthol-induced inhibition of acute respiratory irritation. Aim 2.) Examine the pharmacological effects of menthol and menthol-related compounds on irritant-induced activation of sensory neurons. Aim 3.) Determine the effects of menthol inhalation on smoking-induced lung inflammation and emhysema. Our proposed research will provide new insights into neuronal mechanisms of airway irritation and remodeling, and define a scientific basis for regulatory efforts targeting menthol as a tobacco additive.

项目总结