title: Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels.
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.
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Haoxing
authors.initials: H
authors.lastname: Xu
authors.forename: Markus
authors.initials: M
authors.lastname: Delling
authors.forename: Janice C
authors.initials: JC
authors.lastname: Jun
authors.forename: David E
authors.initials: DE
authors.lastname: Clapham
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D000081007:Cymenes; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005054:Eugenol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D007211:Indoles; D007375:Interleukin-1 / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000166:cytology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000166:cytology*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D013943:Thymol / Q000494:pharmacology*; D014059:Tongue / Q000166:cytology; D014162:Transfection / Q000379:methods
chemical_list: D000081007:Cymenes; D007211:Indoles; D007375:Interleukin-1; D039821:Monoterpenes; D050052:TRPC Cation Channels; D049452:Green Fluorescent Proteins; D013943:Thymol; D005054:Eugenol; C007293:DAPI; C073316:carvacrol