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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleNEUROPHARMACOLOGY

Functional Properties of the High-Affinity TRPV1 (VR1) Vanilloid Receptor Antagonist (4-Hydroxy-5-iodo-3-methoxyphenylacetate ester) Iodo-Resiniferatoxin

Guy R. Seabrook, Kathy G. Sutton, Wolfgang Jarolimek, Gregory J. Hollingworth, Simon Teague, Janine Webb, Natalie Clark, Susan Boyce, Julie Kerby, Zahid Ali, Margaret Chou, Richard Middleton, Gregory Kaczorowski and A. Brian Jones
Journal of Pharmacology and Experimental Therapeutics December 2002, 303 (3) 1052-1060; DOI: https://doi.org/10.1124/jpet.102.040394
Guy R. Seabrook
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathy G. Sutton
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wolfgang Jarolimek
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gregory J. Hollingworth
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon Teague
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Janine Webb
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Natalie Clark
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan Boyce
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julie Kerby
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zahid Ali
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Margaret Chou
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Middleton
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gregory Kaczorowski
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Brian Jones
1 2
  • 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

We have synthesized iodinated resiniferatoxin bearing a 4-hydroxy-5-iodo-3-methoxyphenylacetate ester (I-RTX) and have characterized its activity on rat and human TRPV1 (VR1) receptors, as well as in behavioral assays of nociception. In whole cell patch-clamp recordings from transfected cells the functional activity of I-RTX was determined. Currents activated by capsaicin exhibited characteristic outward rectification and were antagonized by capsazepine and I-RTX. On rat TRPV1 the affinity of I-RTX was 800-fold higher than that of capsazepine (IC50 = 0.7 and 562 nM, respectively) and 10-fold higher on rat versus human receptors (IC50 = 0.7 and 5.4 nM, respectively). The same difference was observed when comparing the inhibition of [3H]RTX binding to rat and human TRPV1 membranes for both RTX and I-RTX. Additional pharmacological differences were revealed using protons as the stimulus. Under these conditions capsazepine only partly blocked currents through rat TRPV1 receptors (by 70 to 80% block), yet was a full antagonist on human receptors. In contrast, I-RTX completely blocked proton-induced currents in both species and that activated by noxious heat. I-RTX also blocked capsaicin-induced firing of C-fibers in a rat in vitro skin-nerve assay. Despite this activity and the high affinity of I-RTX for rat TRPV1, only capsazepine proved to be an effective antagonist of capsaicin-induced paw flinching in rats. Thus, although I-RTX has limited utility for in vivo behavioral studies it is a high-affinity TRPV1 receptor antagonist that will be useful to characterize the functional properties of cloned and native vanilloid receptor subtypes in vitro.

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 303 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 303, Issue 3
1 Dec 2002
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics 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.
Functional Properties of the High-Affinity TRPV1 (VR1) Vanilloid Receptor Antagonist (4-Hydroxy-5-iodo-3-methoxyphenylacetate ester) Iodo-Resiniferatoxin
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleNEUROPHARMACOLOGY

Functional Properties of the High-Affinity TRPV1 (VR1) Vanilloid Receptor Antagonist (4-Hydroxy-5-iodo-3-methoxyphenylacetate ester) Iodo-Resiniferatoxin

Guy R. Seabrook, Kathy G. Sutton, Wolfgang Jarolimek, Gregory J. Hollingworth, Simon Teague, Janine Webb, Natalie Clark, Susan Boyce, Julie Kerby, Zahid Ali, Margaret Chou, Richard Middleton, Gregory Kaczorowski and A. Brian Jones
Journal of Pharmacology and Experimental Therapeutics December 1, 2002, 303 (3) 1052-1060; DOI: https://doi.org/10.1124/jpet.102.040394

Citation Manager Formats

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

Share
Research ArticleNEUROPHARMACOLOGY

Functional Properties of the High-Affinity TRPV1 (VR1) Vanilloid Receptor Antagonist (4-Hydroxy-5-iodo-3-methoxyphenylacetate ester) Iodo-Resiniferatoxin

Guy R. Seabrook, Kathy G. Sutton, Wolfgang Jarolimek, Gregory J. Hollingworth, Simon Teague, Janine Webb, Natalie Clark, Susan Boyce, Julie Kerby, Zahid Ali, Margaret Chou, Richard Middleton, Gregory Kaczorowski and A. Brian Jones
Journal of Pharmacology and Experimental Therapeutics December 1, 2002, 303 (3) 1052-1060; DOI: https://doi.org/10.1124/jpet.102.040394
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
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Iclepertin (BI 425809) in schizophrenia-related models
  • D1 agonist vs. methylphenidate on PFC working memory
  • Obesity Thwarts Preconditioning in TBI
Show more Neuropharmacology

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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

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