Counter-Irritation by Menthol: Molecular Targets and Role in Airway Disease
Principal Investigator: Sven-Eric Jordt
Funding Mechanism: National Institutes of Health- Grant
ID number: 3 R01 HL105635-02S1
Award Date: 9/1/2012
Institution: Yale University
The tobacco industry has added a wide range of chemicals to cigarettes in order to increase product stability and modify taste and sensory qualities. As a cigarette additive, menthol is suspected to accelerate and maintain nicotine dependence and to increase tobacco smoke toxicity; mentholated cigarettes are especially popular with beginning smokers and in minority populations disproportionally affected by chronic obstructive pulmonary disease (COPD), lung cancer and hypertension. Electronic cigarettes (e-cigarettes), rapidly gaining market share as supposedly non-toxic nicotine delivery devices, also contain flavor additives and other chemicals with unknown health effects. The goal of this investigation, which expands ongoing research on menthol, is to reveal how cigarette additives affect respiratory system function and, potentially, promote addiction and lung disease. Investigators will use mouse models and physiological, biochemical, molecular and behavioral approaches to meet the following specific aims: (1) to define the roles of the sensory transient receptor protein channels TRPA1 and TRPM8 in menthol-induced inhibition of acute respiratory irritation; (2) to examine the pharmacological effects of menthol and menthol-related compounds on irritant-induced activation of sensory neurons; (3) to determine the effects of menthol inhalation on smoking-induced lung inflammation and emphysema; and (4) to investigate the sensory and inflammatory effects of e-cigarette aerosols and their chemical additives. This research will provide new insights into neuronal mechanisms of airway irritation and remodeling, and will inform a scientific basis for regulatory efforts targeting menthol and other additives to tobacco cigarettes and e-cigarettes.