Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1

Sven-Eric Jordt, Diana M. Bautista, Huai-hu Chuang, David D. McKemy, Peter M. Zygmunt, Edward D. Högestätt, Ian D. Meng and David Julius ()
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Sven-Eric Jordt: Department of Cellular and Molecular Pharmacology University of California
Diana M. Bautista: Department of Cellular and Molecular Pharmacology University of California
Huai-hu Chuang: Department of Cellular and Molecular Pharmacology University of California
David D. McKemy: Department of Cellular and Molecular Pharmacology University of California
Peter M. Zygmunt: Institute of Laboratory Medicine, Lund University Hospital
Edward D. Högestätt: Institute of Laboratory Medicine, Lund University Hospital
Ian D. Meng: University of California
David Julius: Department of Cellular and Molecular Pharmacology University of California

Nature, 2004, vol. 427, issue 6971, 260-265

Abstract: Abstract Wasabi, horseradish and mustard owe their pungency to isothiocyanate compounds. Topical application of mustard oil (allyl isothiocyanate) to the skin activates underlying sensory nerve endings, thereby producing pain, inflammation and robust hypersensitivity to thermal and mechanical stimuli1,2. Despite their widespread use in both the kitchen and the laboratory, the molecular mechanism through which isothiocyanates mediate their effects remains unknown. Here we show that mustard oil depolarizes a subpopulation of primary sensory neurons that are also activated by capsaicin, the pungent ingredient in chilli peppers, and by Δ9-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Both allyl isothiocyanate and THC mediate their excitatory effects by activating ANKTM1, a member of the TRP ion channel family recently implicated in the detection of noxious cold3,4. These findings identify a cellular and molecular target for the pungent action of mustard oils and support an emerging role for TRP channels as ionotropic cannabinoid receptors5,6,7,8.

Date: 2004
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DOI: 10.1038/nature02282

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