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

Author

Listed:
  • 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
    University of New England)

  • David Julius

    (Department of Cellular and Molecular Pharmacology University of California)

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.

Suggested Citation

  • Sven-Eric Jordt & Diana M. Bautista & Huai-hu Chuang & David D. McKemy & Peter M. Zygmunt & Edward D. Högestätt & Ian D. Meng & David Julius, 2004. "Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1," Nature, Nature, vol. 427(6971), pages 260-265, January.
  • Handle: RePEc:nat:nature:v:427:y:2004:i:6971:d:10.1038_nature02282
    DOI: 10.1038/nature02282
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    Citations

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    Cited by:

    1. Xiaoning Wang & Yangyang Sun & Qian Wang & Fengying Liu & Weijie Yang & Xin Sui & Jun Yang & Minmin Zhang & Shuai Wang & Zhenyu Xiao & Yuan Luo & Yongan Wang & Tong Zhu, 2022. "Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation," IJERPH, MDPI, vol. 19(13), pages 1-18, June.
    2. Barbara Gordon, 2023. "Nutritional Considerations for Bladder Storage Conditions in Adult Females," IJERPH, MDPI, vol. 20(19), pages 1-15, October.
    3. A. Catalina Vélez-Ortega & Ruben Stepanyan & Stephanie E. Edelmann & Sara Torres-Gallego & Channy Park & Desislava A. Marinkova & Joshua S. Nowacki & Ghanshyam P. Sinha & Gregory I. Frolenkov, 2023. "TRPA1 activation in non-sensory supporting cells contributes to regulation of cochlear sensitivity after acoustic trauma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Avnika Bali & Samantha P. Schaefer & Isabelle Trier & Alice L. Zhang & Lilian Kabeche & Candice E. Paulsen, 2023. "Molecular mechanism of hyperactivation conferred by a truncation of TRPA1," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Liying Zhang & Charlotte Simonsen & Lucie Zimova & Kaituo Wang & Lavanya Moparthi & Rachelle Gaudet & Maria Ekoff & Gunnar Nilsson & Ute A. Hellmich & Viktorie Vlachova & Pontus Gourdon & Peter M. Zyg, 2022. "Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    6. Michael A Ha & Gregory J Smith & Joseph A Cichocki & Lu Fan & Yi-Shiuan Liu & Ana I Caceres & Sven Eric Jordt & John B Morris, 2015. "Menthol Attenuates Respiratory Irritation and Elevates Blood Cotinine in Cigarette Smoke Exposed Mice," PLOS ONE, Public Library of Science, vol. 10(2), pages 1-16, February.

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