Journal Club 2014-03-22

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

nature02282

Sven-Eric Jordt1, Diana M. Bautista1, Huai-hu Chuang1,
David D. McKemy1, Peter M. Zygmunt3, Edward D. Ho ̈ gesta ̈ tt3, Ian D. Meng2* & David Julius1

1Department of Cellular and Molecular Pharmacology and 2Department of Neurology, University of California, San Francisco, California 94143-2140, USA 3Department of Clinical Pharmacology, Institute of Laboratory Medicine,
Lund University Hospital, SE-221 85 Lund, Sweden

* Present address: Department of Physiology, College of Osteopathic Medicine, University of New England, 11 Hills Beach Road, Biddeford, Maine 04005, USA ………………………………………………………………………………………………………………………………………………………..

Wasabi, horseradish and mustard owe their pungency to iso- thiocyanate compounds. Topical application of mustard oil (allyl isothiocyanate) to the skin activates underlying sensory nerve endings, thereby producing pain, inflammation and robust

1,2 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 D9-tetrahydrocannabinol (THC), the psycho- active component of marijuana. Both allyl isothiocyanate and THC mediate their excitatory effects by activating ANKTM1, a member of the transient receptor potential (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 receptors5–8.