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 ArticleCellular and Molecular

Mouse Monoclonal Antibodies to Transient Receptor Potential Ankyrin 1 Act as Antagonists of Multiple Modes of Channel Activation

Ki Jeong Lee, Weiya Wang, Rupa Padaki, Vivian Bi, Cherylene A. Plewa and Narender R. Gavva
Journal of Pharmacology and Experimental Therapeutics August 2014, 350 (2) 223-231; DOI: https://doi.org/10.1124/jpet.114.215574
Ki Jeong Lee
Departments of Therapeutic Discovery (K.J.L., R.P., V.B., C.A.P.) and Neuroscience (W.W., N.R.G.), Amgen Inc., Thousand Oaks, California
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Weiya Wang
Departments of Therapeutic Discovery (K.J.L., R.P., V.B., C.A.P.) and Neuroscience (W.W., N.R.G.), Amgen Inc., Thousand Oaks, California
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rupa Padaki
Departments of Therapeutic Discovery (K.J.L., R.P., V.B., C.A.P.) and Neuroscience (W.W., N.R.G.), Amgen Inc., Thousand Oaks, California
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vivian Bi
Departments of Therapeutic Discovery (K.J.L., R.P., V.B., C.A.P.) and Neuroscience (W.W., N.R.G.), Amgen Inc., Thousand Oaks, California
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cherylene A. Plewa
Departments of Therapeutic Discovery (K.J.L., R.P., V.B., C.A.P.) and Neuroscience (W.W., N.R.G.), Amgen Inc., Thousand Oaks, California
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Narender R. Gavva
Departments of Therapeutic Discovery (K.J.L., R.P., V.B., C.A.P.) and Neuroscience (W.W., N.R.G.), Amgen Inc., Thousand Oaks, California
  • 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

The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in different pathophysiologies that include asthma, cough, itch, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and pain behaviors in rodents. Hence, TRPA1 antagonists are being pursued as potential therapeutics. With the goal of generating monoclonal antibodies (mAbs) to human TRPA1 that could act as selective antagonists, we immunized mice with a variety of antigens expressing TRPA1 channels. After generation of hybridomas, the hybridoma conditioned media were screened to identify the mAbs that bind TRPA1 channels by a flow cytometry assay utilizing U2OS or Chinese hamster ovary (CHO) cells stably expressing TRPA1. The purified IgGs from the hybridomas that showed selective binding to TRPA1 were evaluated for antagonism in agonist-induced 45Ca2+ uptake assays using CHO-TRPA1 cells. Several of the mAbs showed concentration-dependent inhibition of AITC and cold (4°C) activation of TRPA1. The most potent mAb, 2B10, had IC50 values of approximately 260 and 90 nM in the two assays, respectively. These antagonist mAbs also blocked osmotically activated TRPA1 as well as activation by an endogenous agonist (4-oxo-2-nonenal). In summary, we generated mouse mAbs against TRPA1 that act as antagonists of multiple modes of TRPA1 activation.

Footnotes

    • Received April 16, 2014.
    • Accepted May 29, 2014.
  • dx.doi.org/10.1124/jpet.114.215574.

  • Copyright © 2014 by 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: 350 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 350, Issue 2
1 Aug 2014
  • 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 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.
Mouse Monoclonal Antibodies to Transient Receptor Potential Ankyrin 1 Act as Antagonists of Multiple Modes of Channel Activation
(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 ArticleCellular and Molecular

Monoclonal Antibodies to TRPA1 Act as Antagonists

Ki Jeong Lee, Weiya Wang, Rupa Padaki, Vivian Bi, Cherylene A. Plewa and Narender R. Gavva
Journal of Pharmacology and Experimental Therapeutics August 1, 2014, 350 (2) 223-231; DOI: https://doi.org/10.1124/jpet.114.215574

Citation Manager Formats

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

Share
Research ArticleCellular and Molecular

Monoclonal Antibodies to TRPA1 Act as Antagonists

Ki Jeong Lee, Weiya Wang, Rupa Padaki, Vivian Bi, Cherylene A. Plewa and Narender R. Gavva
Journal of Pharmacology and Experimental Therapeutics August 1, 2014, 350 (2) 223-231; DOI: https://doi.org/10.1124/jpet.114.215574
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

  • CsA Downregulates Selenop Expression via a STAT3-FoxO1 Axis
  • Anisodamine Ameliorates Acute Lung Injury
  • ACE2 Inhibits LPS-Caused Lung Fibrosis
Show more Cellular and Molecular

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