Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Mechanisms of Transient Receptor Potential Vanilloid 1 Activation and Sensitization by Allyl Isothiocyanate

Maarten Gees, Yeranddy A. Alpizar, Brett Boonen, Alicia Sanchez, Wouter Everaerts, Andrei Segal, Fenqin Xue, Annelies Janssens, Grzegorz Owsianik, Bernd Nilius, Thomas Voets and Karel Talavera
Molecular Pharmacology September 2013, 84 (3) 325-334; DOI: https://doi.org/10.1124/mol.113.085548
Maarten Gees
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yeranddy A. Alpizar
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brett Boonen
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alicia Sanchez
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wouter Everaerts
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrei Segal
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fenqin Xue
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annelies Janssens
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Grzegorz Owsianik
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernd Nilius
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Voets
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karel Talavera
Laboratory for Ion Channel Research, Department of Molecular Cell Biology and TRP Research Platform Leuven (TRPLe) (M.G., Y.A.A., B.B., A.Sa., W.E., A.Se., F.X., A.J., G.O., B.N., T.V., K.T.), and Laboratory of Experimental Urology, Department of Development and Regeneration and TRP Research Platform Leuven (TRPLe) (W.E.), KU Leuven, Leuven, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Allyl isothiocyanate (AITC; aka, mustard oil) is a powerful irritant produced by Brassica plants as a defensive trait against herbivores and confers pungency to mustard and wasabi. AITC is widely used experimentally as an inducer of acute pain and neurogenic inflammation, which are largely mediated by the activation of nociceptive cation channels transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 (TRPV1). Although it is generally accepted that electrophilic agents activate these channels through covalent modification of cytosolic cysteine residues, the mechanism underlying TRPV1 activation by AITC remains unknown. Here we show that, surprisingly, AITC-induced activation of TRPV1 does not require interaction with cysteine residues, but is largely dependent on S513, a residue that is involved in capsaicin binding. Furthermore, AITC acts in a membrane-delimited manner and induces a shift of the voltage dependence of activation toward negative voltages, which is reminiscent of capsaicin effects. These data indicate that AITC acts through reversible interactions with the capsaicin binding site. In addition, we show that TRPV1 is a locus for cross-sensitization between AITC and acidosis in nociceptive neurons. Furthermore, we show that residue F660, which is known to determine the stimulation by low pH in human TRPV1, is also essential for the cross-sensitization of the effects of AITC and low pH. Taken together, these findings demonstrate that not all reactive electrophiles stimulate TRPV1 via cysteine modification and help understanding the molecular bases underlying the surprisingly large role of this channel as mediator of the algesic properties of AITC.

Footnotes

    • Received February 8, 2013.
    • Accepted June 11, 2013.
  • This work was supported by the Belgian Federal Government [Grant IUAP P7/13]; Research Foundation-Flanders [Grants G.0565.07, G.0686.09, and G.A022.11N]; Astellas European Foundation [2009 Award]; and Research Council of KU Leuven [Grants GOA 2009/07, EF/95/010, and PFV/10/006].

  • dx.doi.org/10.1124/mol.113.085548.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 84 (3)
Molecular Pharmacology
Vol. 84, Issue 3
1 Sep 2013
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Mechanisms of Transient Receptor Potential Vanilloid 1 Activation and Sensitization by Allyl Isothiocyanate
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Mechanisms of TRPV1 Modulation by AITC

Maarten Gees, Yeranddy A. Alpizar, Brett Boonen, Alicia Sanchez, Wouter Everaerts, Andrei Segal, Fenqin Xue, Annelies Janssens, Grzegorz Owsianik, Bernd Nilius, Thomas Voets and Karel Talavera
Molecular Pharmacology September 1, 2013, 84 (3) 325-334; DOI: https://doi.org/10.1124/mol.113.085548

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Mechanisms of TRPV1 Modulation by AITC

Maarten Gees, Yeranddy A. Alpizar, Brett Boonen, Alicia Sanchez, Wouter Everaerts, Andrei Segal, Fenqin Xue, Annelies Janssens, Grzegorz Owsianik, Bernd Nilius, Thomas Voets and Karel Talavera
Molecular Pharmacology September 1, 2013, 84 (3) 325-334; DOI: https://doi.org/10.1124/mol.113.085548
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Therapeutic Effects of FGF23 Antagonists in Hyp Mice
  • TRPV3 and TRPV4 Channels Coassemble into Heterotetramers
  • Secretin Amino-Terminal Structure-Activity Relationships and Complementary Mutagenesis at the Site of Docking to the Secretin Receptor
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics