More than cool: promiscuous relationships of menthol and other sensory compounds.
Several temperature-activated transient receptor potential (thermoTRP) ion channels are the molecular receptors of natural compounds that evoke thermal and pain sensations. Menthol, popularly known for its cooling effect, activates TRPM8--a cold-activated thermoTRP ion channel. However, human physiological studies demonstrate a paradoxical role of menthol in modulation of warm sensation, and here, we show that menthol also activates heat-activated TRPV3. We further show that menthol inhibits TRPA1, potentially explaining the use of menthol as an analgesic. Similar to menthol, both camphor and cinnamaldehyde (initially reported to be specific activators of TRPV3 and TRPA1, respectively) also modulate other thermoTRPs. Therefore, we find that many "sensory compounds" presumed to be specific have a promiscuous relationship with thermoTRPs.
Macpherson
Lindsey J
LJ
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hwang
Sun Wook
SW
Miyamoto
Takashi
T
Dubin
Adrienne E
AE
Patapoutian
Ardem
A
Story
Gina M
GM
D000818:Animals; D000831:Animals, Newborn; D000982:Antipruritics / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002164:Camphor / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003952:Diagnostic Imaging / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology; D015603:Keratinocytes; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008610:Menthol / Q000494:pharmacology*; D051379:Mice; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D013696:Temperature; D014162:Transfection / Q000379:methods; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000502:physiology
D000982:Antipruritics; D050051:Transient Receptor Potential Channels; D008610:Menthol; D002164:Camphor; D002211:Capsaicin; D002118:Calcium