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.
Bibliographical noteFunding Information:
We thank H. Hu and T. Earley for the technical assistance. This work was supported by NINDS grants NS046303 and NS04910. A.P. is a Damon Runyon Fellow and a member of the H. Dorris Neurological Research Institute. G.S. is a recipient of an NRSA postdoctoral fellowship from NIH (NS047911).
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology