Nicotine activates the chemosensory cation channel TRPA1

Karel Talavera, Maarten Gees, Yuji Karashima, Víctor M. Meseguer, Jeroen A.J. Vanoirbeek, Nils Damann, Wouter Everaerts, Melissa Benoit, Annelies Janssens, Rudi Vennekens, Félix Viana, Benoit Nemery, Bernd Nilius, Thomas Voets

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172 Citations (Scopus)

Abstract

Topical application of nicotine, as used in nicotine replacement therapies, causes irritation of the mucosa and skin. This reaction has been attributed to activation of nicotinic acetylcholine receptors (nAChRs) in chemosensory neurons. In contrast with this view, we found that the chemosensory cation channel transient receptor potential A1 (TRPA1) is crucially involved in nicotine-induced irritation. We found that micromolar concentrations of nicotine activated heterologously expressed mouse and human TRPA1. Nicotine acted in a membrane-delimited manner, stabilizing the open state(s) and destabilizing the closed state(s) of the channel. In the presence of the general nAChR blocker hexamethonium, nociceptive neurons showed nicotine-induced responses that were strongly reduced in TRPA1-deficient mice. Finally, TRPA1 mediated the mouse airway constriction reflex to nasal instillation of nicotine. The identification of TRPA1 as a nicotine target suggests that existing models of nicotine-induced irritation should be revised and may facilitate the development of smoking cessation therapies with less adverse effects.

Original languageEnglish
Pages (from-to)1293-1299
Number of pages7
JournalNature Neuroscience
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 1 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Talavera, K., Gees, M., Karashima, Y., Meseguer, V. M., Vanoirbeek, J. A. J., Damann, N., Everaerts, W., Benoit, M., Janssens, A., Vennekens, R., Viana, F., Nemery, B., Nilius, B., & Voets, T. (2009). Nicotine activates the chemosensory cation channel TRPA1. Nature Neuroscience, 12(10), 1293-1299. https://doi.org/10.1038/nn.2379