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 ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Protease-Activated Receptor-2 Peptides Activate Neurokinin-1 Receptors in the Mouse Isolated Trachea

Hugh T. Abey, David P. Fairlie, James D. Moffatt, Rowan W. Balzary and Thomas M. Cocks
Journal of Pharmacology and Experimental Therapeutics May 2006, 317 (2) 598-605; DOI: https://doi.org/10.1124/jpet.105.097121
Hugh T. Abey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David P. Fairlie
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James D. Moffatt
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rowan W. Balzary
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas M. Cocks
  • 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

Protective roles for protease-activated receptor-2 (PAR2) in the airways including activation of epithelial chloride (Cl–) secretion are based on the use of presumably PAR2-selective peptide agonists. To determine whether PAR2 peptide-activated Cl– secretion from mouse tracheal epithelium is dependent on PAR2, changes in ion conductance across the epithelium [short-circuit current (ISC)] to PAR2 peptides were measured in Ussing chambers under voltage clamp. In addition, epithelium- and endothelium-dependent relaxations to these peptides were measured in two established PAR2 bioassays, isolated ring segments of mouse trachea and rat thoracic aorta, respectively. Apical application of the PAR2 peptide SLIGRL caused increases in ISC, which were inhibited by three structurally different neurokinin receptor-1 (NK1R) antagonists and inhibitors of Cl– channels but not by capsaicin, the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP8–37, or the nonselective cyclooxygenase inhibitor indomethacin. Only high concentrations of trypsin caused an increase in ISC but did not affect the responses to SLIGRL. Relaxations to SLIGRL in the trachea and aorta were unaffected by the NK1R antagonist nolpitantium (SR 140333) but were abolished by trypsin desensitization. The rank order of potency for a range of peptides in the trachea ISC assay was 2-furoyl-LIGRL > SLCGRL > SLIGRL = SLIGRT > LSIGRL compared with 2-furoyl-LIGRL > SLIGRL > SLIGRT > SLCGRL (LSIGRL inactive) in the aorta relaxation assay. In the mouse trachea, PAR2 peptides activate both epithelial NK1R coupled to Cl– secretion and PAR2 coupled to prostaglandin E2-mediated smooth muscle relaxation. Such a potential lack of specificity of these commonly used peptides needs to be considered when roles for PAR2 in airway function in health and disease are determined.

Footnotes

  • This work was supported by the National Health and Medical Research Council of Australia.

  • doi:10.1124/jpet.105.097121.

  • ABBREVIATIONS: PAR2, protease-activated receptor(s)-2; PGE2, prostaglandin E2; SR 140333, nolpitantium; GR205171, 3(S)-(2-methoxy-5-(5-trifluoromethyltetrazol-1-yl)-phenylmethylamino)-2(S)-phenylpiperidine; GR82334, d-Pro(9)-[spiro-gamma-lactam]-Leu(10)-Trp(11)-physalaemin-(1-11); DIDS, 4,4-diisothio-cyanostilbene-2,2-disulfonic acid; NK1R, neurokinin-1 receptor(s); CGRP, calcitonin gene-related peptide; ISC, short-circuit current; ANOVA, analysis of variance.

    • Received October 13, 2005.
    • Accepted January 3, 2006.
  • 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.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
  • 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.
Protease-Activated Receptor-2 Peptides Activate Neurokinin-1 Receptors in the Mouse Isolated Trachea
(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 ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Protease-Activated Receptor-2 Peptides Activate Neurokinin-1 Receptors in the Mouse Isolated Trachea

Hugh T. Abey, David P. Fairlie, James D. Moffatt, Rowan W. Balzary and Thomas M. Cocks
Journal of Pharmacology and Experimental Therapeutics May 1, 2006, 317 (2) 598-605; DOI: https://doi.org/10.1124/jpet.105.097121

Citation Manager Formats

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

Share
Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Protease-Activated Receptor-2 Peptides Activate Neurokinin-1 Receptors in the Mouse Isolated Trachea

Hugh T. Abey, David P. Fairlie, James D. Moffatt, Rowan W. Balzary and Thomas M. Cocks
Journal of Pharmacology and Experimental Therapeutics May 1, 2006, 317 (2) 598-605; DOI: https://doi.org/10.1124/jpet.105.097121
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
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Lipopolysaccharide Induces Epithelium- and Prostaglandin E2-Dependent Relaxation of Mouse Isolated Trachea through Activation of Cyclooxygenase (COX)-1 and COX-2
  • Cannabinoid-Mediated Elevation of Intracellular Calcium: A Structure-Activity Relationship
Show more INFLAMMATION AND IMMUNOPHARMACOLOGY

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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics