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

Neurokinin-3 Receptor-Specific Antagonists Talnetant and Osanetant Show Distinct Mode of Action in Cellular Ca2+ Mobilization but Display Similar Binding Kinetics and Identical Mechanism of Binding in Ligand Cross-Competition

Gaochao Tian, Dee Wilkins and Clay W. Scott
Molecular Pharmacology March 2007, 71 (3) 902-911; DOI: https://doi.org/10.1124/mol.106.029868
Gaochao Tian
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dee Wilkins
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clay W. Scott
  • 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

Talnetant and osanetant, two structurally diverse antagonists of neurokinin-3 receptor (NK3), displayed distinct modes of action in Ca2+ mobilization. Although talnetant showed a normal Schild plot with a slope close to unity and a Kb similar to its Ki value in binding, osanetant presented an aberrant Schild with a steep slope (3.3 ± 0.5) and a Kb value (12 nM) significantly elevated compared with its Ki value (0.8 nM) in binding. Kinetic binding experiments indicated a simple one-step binding mechanism with relatively fast on- and off-rates for both antagonists, arguing against slow onset of antagonism as the reason for abnormal Schild. This conclusion was supported by prolonged preincubation of antagonist that failed to improve the observed aberrant Schild. In ligand cross-competition binding, both talnetant and osanetant displayed linear reciprocal plots of identical slope when [MePhe7]neurokinin B (NKB) was used as the other competition partner with 125I-[MePhe7]NKB as the radioligand, indicating competitive binding of either antagonist with regard to [MePhe7]NKB. Similar patterns were obtained when talnetant was tested against osanetant, indicating competitive binding between the two antagonists as well. These results were reproduced when [3H]4-quinolinecarboxamide (SB222200), a close derivative of talnetant, was used as the radioligand. Taken together, these data strongly suggest binding of both talnetant and osanetant at the orthosteric binding site with similar kinetic properties and do not support the hypothesis that the aberrant Schild observed in functional assays for osanetant is derived from differences in the mechanism of binding for these NK3 antagonists.

Footnotes

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

  • doi:10.1124/mol.106.029868.

  • ABBREVIATIONS: NK, neurokinin; NKB, neurokinin B; BSA, bovine serum albumin; D2, dopamine receptor 2; SPA, scintillation proximity assay; CHO, Chinese hamster ovary.

    • Received August 11, 2006.
    • Accepted December 15, 2006.
  • 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: 71 (3)
Molecular Pharmacology
Vol. 71, Issue 3
1 Mar 2007
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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.
Neurokinin-3 Receptor-Specific Antagonists Talnetant and Osanetant Show Distinct Mode of Action in Cellular Ca2+ Mobilization but Display Similar Binding Kinetics and Identical Mechanism of Binding in Ligand Cross-Competition
(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

Neurokinin-3 Receptor-Specific Antagonists Talnetant and Osanetant Show Distinct Mode of Action in Cellular Ca2+ Mobilization but Display Similar Binding Kinetics and Identical Mechanism of Binding in Ligand Cross-Competition

Gaochao Tian, Dee Wilkins and Clay W. Scott
Molecular Pharmacology March 1, 2007, 71 (3) 902-911; DOI: https://doi.org/10.1124/mol.106.029868

Citation Manager Formats

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

Share
Research ArticleArticle

Neurokinin-3 Receptor-Specific Antagonists Talnetant and Osanetant Show Distinct Mode of Action in Cellular Ca2+ Mobilization but Display Similar Binding Kinetics and Identical Mechanism of Binding in Ligand Cross-Competition

Gaochao Tian, Dee Wilkins and Clay W. Scott
Molecular Pharmacology March 1, 2007, 71 (3) 902-911; DOI: https://doi.org/10.1124/mol.106.029868
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
    • Appendix: Derivation of Equation 1 for Ligand Cross-Competition
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
  • Benzbromarone relaxes airway smooth muscle via BK activation
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics