Title: Nicotine activates the chemosensory cation channel TRPA1
Authors: Talavera PĂ©rez, Karel ×
Gees, Maarten
Karashima, Yuji
Meseguer, Víctor M
Vanoirbeek, Jeroen
Damann, Nils
Everaerts, Wouter
Benoit, Melissa
Janssens, Annelies
Vennekens, Rudi
Viana, Félix
Nemery, Benoit
Nilius, Bernd
Voets, Thomas #
Issue Date: Oct-2009
Publisher: Nature America Inc.
Series Title: Nature Neuroscience vol:12 issue:10 pages:1293-1299
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.
ISSN: 1097-6256
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Occupational, Environmental and Insurance Medicine (-)
Laboratory of Ion Channel Research
Physiology Section (-)
Environment and Health - miscellaneous
Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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