Camphor activates and sensitizes transient receptor potential melastatin 8 (TRPM8) to cooling and icilin.

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Selescu T, Ciobanu AC, Dobre C, Reid G, Babes A

Camphor activates and sensitizes transient receptor potential melastatin 8 (TRPM8) to cooling and icilin.

Chem Senses. 2013 Sep;38(7):563-75. doi: 10.1093/chemse/bjt027. Epub 2013 Jul 4.

PubMed ID

23828908 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drugs

(S)-camphor

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
(S)-camphor	Transient receptor potential cation channel subfamily M member 8	Protein	Humans	Yes	Activator	Details
Camphor	Transient receptor potential cation channel subfamily M member 8	Protein	Humans	Yes	Activator	Details