Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.
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.
Jordt
Sven-Eric
SE
Department of Cellular and Molecular Pharmacology University of California, San Francisco, California 94143-2140, USA.
Bautista
Diana M
DM
Chuang
Huai-Hu
HH
McKemy
David D
DD
Zygmunt
Peter M
PM
Högestätt
Edward D
ED
Meng
Ian D
ID
Julius
David
D
D000818:Animals; D000831:Animals, Newborn; D017487:Ankyrins; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002186:Cannabinoids / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D013759:Dronabinol / Q000494:pharmacology; D006801:Humans; D009149:Mustard Plant; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010938:Plant Oils / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D019284:Thapsigargin / Q000494:pharmacology; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D012668:Trigeminal Ganglion
D017487:Ankyrins; D015220:Calcium Channels; D002186:Cannabinoids; D009419:Nerve Tissue Proteins; D010938:Plant Oils; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels; C480976:Trpa1 protein, rat; D019284:Thapsigargin; D013759:Dronabinol; D002217:Carbachol; D002211:Capsaicin