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

Author: Jordt, Sven-Eric; Bautista, Diana M.; Chuang, Huai-Hu; McKemy, David D.; Zygmunt, Peter M.; Hogestatt, Edward D.; Meng, Ian D.; Julius, David

Description: 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 stimuli. 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 Delta(9)-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 cold. 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 receptors.

Subject headings: Animals; Animals; Newborn; Ankyrins; Calcium Channels; Calcium Signaling; Cannabinoids; Capsaicin; Carbachol; Cells; Cultured; Cloning; Molecular; Dronabinol; Humans; Mustard Plant; Nerve Tissue Proteins; Neurons; Afferent; Nociceptors; Oocytes; Plant Oils; RNA; Messenger; Rats; Rats; Sprague-Dawley; TRPA1 Cation Channel; TRPC Cation Channels; Thapsigargin; Transient Receptor Potential Channels; Trigeminal Ganglion

Publication year: 2004

Journal or book title: Nature

Volume: 427

Issue: 6971

Pages: 260-265

Find the full text: https://www.nature.com/articles/nature02282

Find more like this one (cited by): https://scholar.google.com/scholar?cites=14288452983170524527&as_sdt=5,26&sciodt=0,26&hl=en

Serial number: 3275

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