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 Ca21-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 Ca21 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.