Abstract
Carvacrol, eugenol and thymol are major components of plants such as oregano, savory, clove and thyme. When applied to the tongue, these flavors elicit a warm sensation. They are also known to be skin sensitizers and allergens. The transient receptor potential channel (TRPV3) is a warm-sensitive Ca2+-permeable cation channel highly expressed in the skin, tongue and nose. Here we show that TRPV3 is strongly activated and sensitized by carvacrol, thymol and eugenol. Tongue and skin epithelial cells respond to carvacrol and eugenol with an increase in intracellular Ca2+ levels. We also show that this TRPV3 activity is strongly potentiated by phospholipase C–linked, G protein–coupled receptor stimulation. In addition, carvacrol activates and rapidly desensitizes TRPA1, which may explain the pungency of oregano. Our results support a role for temperature-sensitive TRP channels in chemesthesis in oral and nasal epithelium and suggest that TRPV3 may be a molecular target of plant-derived skin sensitizers.
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Acknowledgements
This work was supported by the Sandler Program for Ashma Research and the Howard Hughes Medical Institute. We thank S.H. Yuspa (National Cancer Institute) for providing us with mouse 308 keratinocytes. We thank D. Julius for rat TRPV1, TRPV2, TRPM8 and TRPA1 constructs. M. Caterina and D. Ren provided the mouse TRPV3 and TRPV4 constructs, respectively. We are grateful to U. Berger and H. Wang for assistance. We thank S. Cibulsky, N. Blair, B. Carter, W. Pu, S. Ikeda, C. Medler, S. Roper and members of the Clapham laboratory for discussion and helpful comments.
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Supplementary information
Supplementary Fig. 1
Specificity of mTRPV3 polyclonal antibody. (PDF 523 kb)
Supplementary Fig. 2
TRPV3 expression in the epithelia surrounding taste buds of circumvallate papillae. (PDF 2120 kb)
Supplementary Fig. 3
Structures of a family of plant-derived phenol-containing compounds. (PDF 16 kb)
Supplementary Fig. 4
Carvacrol increases [Ca2+]i in rat tongue epithelial cells. (PDF 43 kb)
Supplementary Fig. 5
Carvacrol does not activate TRPV1, TRPV2, TRPV4, or TRPM8. (PDF 1027 kb)
Supplementary Fig. 6
Mouse 308 keratinocytes express TRPV3 and display TRPV3-like (ITRPV3_L) currents. (PDF 810 kb)
Supplementary Fig. 7
Eugenol activates TRPV3 but not TRPV2 or TRPV4. (PDF 1596 kb)
Supplementary Fig. 8
Sensitization of ITRPV3 by stimulation of G protein-linked, PLC-coupled receptors. (PDF 784 kb)
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Xu, H., Delling, M., Jun, J. et al. Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neurosci 9, 628–635 (2006). https://doi.org/10.1038/nn1692
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DOI: https://doi.org/10.1038/nn1692
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