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

Selective and Potent Agonists and Antagonists for Investigating the Role of Mouse Oxytocin Receptors

Marta Busnelli, Elisabetta Bulgheroni, Maurice Manning, Gunnar Kleinau and Bice Chini
Journal of Pharmacology and Experimental Therapeutics August 2013, 346 (2) 318-327; DOI: https://doi.org/10.1124/jpet.113.202994
Marta Busnelli
CNR, Institute of Neuroscience, Milan, Italy (M.B., E.B., B.C.); Department of Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy (M.B.); Department of Biochemistry and Cancer Biology, University of Toledo, Toledo, Ohio (M.M.); and Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany (G.K.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elisabetta Bulgheroni
CNR, Institute of Neuroscience, Milan, Italy (M.B., E.B., B.C.); Department of Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy (M.B.); Department of Biochemistry and Cancer Biology, University of Toledo, Toledo, Ohio (M.M.); and Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany (G.K.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maurice Manning
CNR, Institute of Neuroscience, Milan, Italy (M.B., E.B., B.C.); Department of Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy (M.B.); Department of Biochemistry and Cancer Biology, University of Toledo, Toledo, Ohio (M.M.); and Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany (G.K.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gunnar Kleinau
CNR, Institute of Neuroscience, Milan, Italy (M.B., E.B., B.C.); Department of Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy (M.B.); Department of Biochemistry and Cancer Biology, University of Toledo, Toledo, Ohio (M.M.); and Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany (G.K.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bice Chini
CNR, Institute of Neuroscience, Milan, Italy (M.B., E.B., B.C.); Department of Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy (M.B.); Department of Biochemistry and Cancer Biology, University of Toledo, Toledo, Ohio (M.M.); and Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany (G.K.)
  • 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 neuropeptides oxytocin (OT) and vasopressin (AVP) have been shown to play a central role in social behaviors; as a consequence, they have been recognized as potential drugs to treat neurodevelopmental and psychiatric disorders characterized by impaired social interactions. However, despite the basic and preclinical relevance of mouse strains carrying genetic alterations in the OT/AVP systems to basic and preclinical translational neuroscience, the pharmacological profile of mouse OT/AVP receptor subtypes has not been fully characterized. To fill in this gap, we have characterized a number of OT and AVP agonists and antagonists at three murine OT/AVP receptors expressed in the nervous system as follows: the oxytocin (mOTR) and vasopressin V1a (mV1aR) and V1b (mV1bR) subtypes. These three receptors were transiently expressed in vitro for binding and intracellular signaling assays, and then a homology model of the mOTR structure was constructed to investigate how its molecular features compare with human and rat OTR orthologs. Our data indicate that the selectivity profile of the natural ligands, OT and AVP, is conserved in humans, rats, and mice. Furthermore, we found that the synthetic peptide [Thr4Gly7]OT (TGOT) is remarkably selective for the mOTR and, like the endogenous OT ligand, activates Gq and Gi and recruits β-arrestins. Finally, we report three antagonists that exhibit remarkably high affinities and selectivities at mOTRs. These highly selective pharmacological tools will contribute to the investigation of the specific physiologic and pathologic roles of mOTR for the development of selective OT-based therapeutics.

Footnotes

    • Received January 8, 2013.
    • Accepted May 29, 2013.
  • This study was supported by Cariplo Foundation (Grant 2008.2314), Regione Lombardia (Progetto TerDisMental, ID 16983–Rif. SAL-50), and Telethon Foundation (Grant GGP12207).

  • dx.doi.org/10.1124/jpet.113.202994.

  • Copyright © 2013 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: 346 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 346, Issue 2
1 Aug 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 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.
Selective and Potent Agonists and Antagonists for Investigating the Role of Mouse Oxytocin Receptors
(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

Identification of Selective and Potent Analogs of Mouse OTR

Marta Busnelli, Elisabetta Bulgheroni, Maurice Manning, Gunnar Kleinau and Bice Chini
Journal of Pharmacology and Experimental Therapeutics August 1, 2013, 346 (2) 318-327; DOI: https://doi.org/10.1124/jpet.113.202994

Citation Manager Formats

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

Share
Research ArticleNeuropharmacology

Identification of Selective and Potent Analogs of Mouse OTR

Marta Busnelli, Elisabetta Bulgheroni, Maurice Manning, Gunnar Kleinau and Bice Chini
Journal of Pharmacology and Experimental Therapeutics August 1, 2013, 346 (2) 318-327; DOI: https://doi.org/10.1124/jpet.113.202994
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
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Substituted tryptamine activity at 5-HT receptors & SERT
  • In Vivo SRI-32743 Attenuates Tat Effects on Extracellular DA
  • Kv7 Opener Attenuates Seizures and Cognitive Deficit
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics