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Bimodal Action of Menthol on the Transient Receptor Potential Channel TRPA1
Abstract
TRPA1 is a calcium-permeable nonselective cation transient receptor potential (TRP) channel that functions as an excitatory ionotropic receptor in nociceptive neurons. TRPA1 is robustly activated by pungent substances in mustard oil, cinnamon, and garlic and mediates the inflammatory actions of environmental irritants and proalgesic agents. Here, we demonstrate a bimodal sensitivity of TRPA1 to menthol, a widely used cooling agent and known activator of the related cold receptor TRPM8. In whole-cell and single-channel recordings of heterologously expressed TRPA1, submicromolar to low-micromolar concentrations of menthol cause channel activation, whereas higher concentrations lead to a reversible channel block. In addition, we provide evidence for TRPA1-mediated menthol responses in mustard oil-sensitive trigeminal ganglion neurons. Our data indicate that TRPA1 is a highly sensitive menthol receptor that very likely contributes to the diverse psychophysical sensations after topical application of menthol to the skin or mucous membranes of the oral and nasal cavities.
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“As suggested, TRPA1-mediated depolarization of ICCs does not necessarily result in an overall increase in smooth muscle contractility, rather, this study helps in our understanding of the multiple targets of menthol in the GI tract, suggesting that its net effect derives from the balance between inhibitory pathways, e.g., Ca2+ channel blockade and transient receptor potential cation channel sub”
From Natural Remedies for Irritable Bowel Syndrome: A Comprehensive Review of Herbal-Based Therapies (2025) · cites this paper as [64]
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Cited by
Cellular and Molecular Mechanisms of Pain
Basbaum, A. I., Bautista, D. M., Scherrer, G., & Julius, D. (2009) · Cell · doi:10.1016/j.cell.2009.09.028 · Cited by 4,344
TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
Meseguer, V., Alpizar, Y. A., Luis, E., Tajada, S., Denlinger, B., Fajardo, O., Manenschijn, J.-A., Fernández-Peña, C., Talavera, A., Kichko, T., et al. (2014) · Nature Communications · doi:10.1038/ncomms4125 · Cited by 479
Self-citationTRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain
Liu, B., Fan, L., Balakrishna, S., Sui, A., Morris, J. B., & Jordt, S.-E. (2013) · Pain · doi:10.1016/j.pain.2013.06.043 · Cited by 319
Chemosensory properties of the trigeminal system
Viana, F. (2011) · ACS Chemical Neuroscience · doi:10.1021/cn100102c · Cited by 196
Weerts, Z. Z. R. M., Masclee, A. A. M., Witteman, B. J. M., Clemens, C. H. M., Winkens, B., Brouwers, J. R. B. J., Frijlink, H. W., Muris, J. W. M., De Wit, N. J., Essers, B. A. B., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.08.026 · Cited by 137
Metadata
- Authors
- Karashima, Y., Damann, N., Prenen, J., Talavera, K., Segal, A., Voets, T., & Nilius, B.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-09-12
- Volume
- 27
- Issue
- 37
- Pages
- 9874-9884
- ISSN
- 0270-6474
- 1529-2401
- Cited by
- 477
- References
- 0
- Language
- en
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