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Camphor activates and sensitizes transient receptor potential melastatin 8 (TRPM8) to cooling and icilin.
Chem Senses. 2013 Sep; 38(7):563-75.CS

Abstract

Camphor is known to potentiate both heat and cold sensations. Although the sensitization to heat could be explained by the activation of heat-sensitive transient receptor potential (TRP) channels TRPV1 and TRPV3, the camphor-induced sensitization to cooling remains unexplained. In this study, we present evidence for the activation of the cold- and menthol-sensitive channel transient receptor potential melastatin 8 (TRPM8) by camphor. Calcium transients evoked by camphor in HEK293 cells expressing human and rat TRPM8 are inhibited by the TRPM8 antagonists 4-(3-chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide and 2-aminoethyl diphenylborinate. Camphor also sensitized the cold-induced calcium transients and evoked desensitizing outward-rectifying currents in TRPM8-expressing HEK293 cells. In the presence of ruthenium red (a blocker of TRPV1, TRPV3, and TRPA1), the camphor sensitivity of cultured rat dorsal root ganglion neurons was highest in a subpopulation of cold- and icilin-sensitive neurons, strongly suggesting that camphor activates native TRPM8. Camphor has a dual action on TRPM8: it not only activates the channel but also inhibits its response to menthol. The icilin-insensitive chicken TRPM8 was also camphor insensitive. However, camphor was able to activate an icilin-insensitive human TRPM8 mutant channel. The activation and sensitization to cold of mammalian TRPM8 are likely to be responsible for the psychophysical enhancement of innocuous cold and "stinging/burning" cold sensations by camphor.

Authors+Show Affiliations

Department of Anatomy, Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania. tudorselescu@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23828908

Citation

Selescu, Tudor, et al. "Camphor Activates and Sensitizes Transient Receptor Potential Melastatin 8 (TRPM8) to Cooling and Icilin." Chemical Senses, vol. 38, no. 7, 2013, pp. 563-75.
Selescu T, Ciobanu AC, Dobre C, et al. Camphor activates and sensitizes transient receptor potential melastatin 8 (TRPM8) to cooling and icilin. Chem Senses. 2013;38(7):563-75.
Selescu, T., Ciobanu, A. C., Dobre, C., Reid, G., & Babes, A. (2013). Camphor activates and sensitizes transient receptor potential melastatin 8 (TRPM8) to cooling and icilin. Chemical Senses, 38(7), 563-75. https://doi.org/10.1093/chemse/bjt027
Selescu T, et al. Camphor Activates and Sensitizes Transient Receptor Potential Melastatin 8 (TRPM8) to Cooling and Icilin. Chem Senses. 2013;38(7):563-75. PubMed PMID: 23828908.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Camphor activates and sensitizes transient receptor potential melastatin 8 (TRPM8) to cooling and icilin. AU - Selescu,Tudor, AU - Ciobanu,Alexandru C, AU - Dobre,Cristian, AU - Reid,Gordon, AU - Babes,Alexandru, Y1 - 2013/07/04/ PY - 2013/7/6/entrez PY - 2013/7/6/pubmed PY - 2014/4/4/medline KW - chicken TRPM8 KW - dorsal root ganglion KW - eucalyptol KW - human TRPM8 KW - icilin KW - menthol SP - 563 EP - 75 JF - Chemical senses JO - Chem Senses VL - 38 IS - 7 N2 - Camphor is known to potentiate both heat and cold sensations. Although the sensitization to heat could be explained by the activation of heat-sensitive transient receptor potential (TRP) channels TRPV1 and TRPV3, the camphor-induced sensitization to cooling remains unexplained. In this study, we present evidence for the activation of the cold- and menthol-sensitive channel transient receptor potential melastatin 8 (TRPM8) by camphor. Calcium transients evoked by camphor in HEK293 cells expressing human and rat TRPM8 are inhibited by the TRPM8 antagonists 4-(3-chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide and 2-aminoethyl diphenylborinate. Camphor also sensitized the cold-induced calcium transients and evoked desensitizing outward-rectifying currents in TRPM8-expressing HEK293 cells. In the presence of ruthenium red (a blocker of TRPV1, TRPV3, and TRPA1), the camphor sensitivity of cultured rat dorsal root ganglion neurons was highest in a subpopulation of cold- and icilin-sensitive neurons, strongly suggesting that camphor activates native TRPM8. Camphor has a dual action on TRPM8: it not only activates the channel but also inhibits its response to menthol. The icilin-insensitive chicken TRPM8 was also camphor insensitive. However, camphor was able to activate an icilin-insensitive human TRPM8 mutant channel. The activation and sensitization to cold of mammalian TRPM8 are likely to be responsible for the psychophysical enhancement of innocuous cold and "stinging/burning" cold sensations by camphor. SN - 1464-3553 UR - https://www.unboundmedicine.com/medline/citation/23828908/Camphor_activates_and_sensitizes_transient_receptor_potential_melastatin_8__TRPM8__to_cooling_and_icilin_ DB - PRIME DP - Unbound Medicine ER -