Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Allosteric Effects of G Protein Overexpression on the Binding of β-Adrenergic Ligands with Distinct Inverse Efficacies

Mounia Azzi, Graciela Piñeyro, Stéphanie Pontier, Stéphane Parent, Hervé Ansanay and Michel Bouvier
Molecular Pharmacology November 2001, 60 (5) 999-1007; DOI: https://doi.org/10.1124/mol.60.5.999
Mounia Azzi
Département de Biochimie and le Groupe de Recherches sur le Système Nerveux Autonome, Université de Montréal, Montréal, Québec, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Graciela Piñeyro
Département de Biochimie and le Groupe de Recherches sur le Système Nerveux Autonome, Université de Montréal, Montréal, Québec, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stéphanie Pontier
Département de Biochimie and le Groupe de Recherches sur le Système Nerveux Autonome, Université de Montréal, Montréal, Québec, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stéphane Parent
Département de Biochimie and le Groupe de Recherches sur le Système Nerveux Autonome, Université de Montréal, Montréal, Québec, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hervé Ansanay
Département de Biochimie and le Groupe de Recherches sur le Système Nerveux Autonome, Université de Montréal, Montréal, Québec, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michel Bouvier
Département de Biochimie and le Groupe de Recherches sur le Système Nerveux Autonome, Université de Montréal, Montréal, Québec, Canada
  • 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

Allosteric models of G protein-coupled receptors predict that G protein influences the spontaneous isomerization between inactive (R) and active (R*) conformations. Since inverse agonists have been proposed to preferentially bind to the inactive and uncoupled form(s), changes in the G protein content should influence the binding properties of these ligands. To test this hypothesis, we systematically assessed the effect of G proteins on the binding of β2-adrenergic ligands with distinct levels of inverse efficacy. Recombinant baculoviruses encoding the human β2-adrenoreceptor (β2AR) were expressed alone or in combination with G protein subunits in Sf9 cells. Coexpression with the G protein αsβ1γ2 did not influence the relative efficacy of the ligands to inhibit the adenylyl cyclase but induced considerable decrease in number of sites detected by [3H]ICI 118551, [3H]propranolol, and125I-cyanopindolol. This loss was proportional to the inverse efficacy of the ligand used as the radiotracer in the assay. The addition of Gpp(NH)p inhibited the effects of G protein overexpression indicating that the G proteins acted allosterically. Consistent with this notion, Western blot analysis revealed that coexpression with the G proteins was not accompanied by a loss of immunoreactive β2AR. Such allosteric effects of the G proteins were also observed in mammalian cells expressing endogenous level of G proteins indicating that the phenomenon is not unique to overexpression systems. Taken together, these results demonstrate that the apparent receptor number detected by radiolabeled inverse agonists is affected by the content in G proteins as a result of their influence on R/R* isomerization.

  • 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: 60 (5)
Molecular Pharmacology
Vol. 60, Issue 5
1 Nov 2001
  • Table of Contents
  • About the Cover
  • Index by author
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.
Allosteric Effects of G Protein Overexpression on the Binding of β-Adrenergic Ligands with Distinct Inverse Efficacies
(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

Allosteric Effects of G Protein Overexpression on the Binding of β-Adrenergic Ligands with Distinct Inverse Efficacies

Mounia Azzi, Graciela Piñeyro, Stéphanie Pontier, Stéphane Parent, Hervé Ansanay and Michel Bouvier
Molecular Pharmacology November 1, 2001, 60 (5) 999-1007; DOI: https://doi.org/10.1124/mol.60.5.999

Citation Manager Formats

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

Allosteric Effects of G Protein Overexpression on the Binding of β-Adrenergic Ligands with Distinct Inverse Efficacies

Mounia Azzi, Graciela Piñeyro, Stéphanie Pontier, Stéphane Parent, Hervé Ansanay and Michel Bouvier
Molecular Pharmacology November 1, 2001, 60 (5) 999-1007; DOI: https://doi.org/10.1124/mol.60.5.999
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of Celecoxib targets by label-free TPP
  • Editing TOP2α Intron 19 5′ SS Circumvents Drug Resistance
  • CTS Bias
Show more Article

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics