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

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.

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Figure 1: THC and mustard oil activate a subset of sensory neurons.
Figure 2: Activation of ANKTM1 by mustard oils in transfected mammalian cells and Xenopus oocytes.
Figure 3: Activation of ANKTM1 by cannabinoids.
Figure 4: ANKTM1 is a receptor-operated channel.

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Acknowledgements

We are grateful to G. Hollopeter for generation of the adult rat trigeminal cDNA library and to B. Trueb for providing us with human ANKTM1 cDNA. This work was supported by grants from the Segerfalk Foundation and the Swedish Research Council (P.Z. and E.H.), the American Heart Association (H.C.) and the National Institutes of Health (I.M., D.B. and D.J.).

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Correspondence to David Julius.

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Jordt, S., Bautista, D., Chuang, H. et al. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427, 260–265 (2004). https://doi.org/10.1038/nature02282

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