Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • 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

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
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • 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

The Third Extracellular Loop of the β2-Adrenergic Receptor Can Modulate Receptor/G Protein Affinity

Ming-Ming Zhao, Robert J. Gaivin and Dianne M. Perez
Molecular Pharmacology March 1998, 53 (3) 524-529; DOI: https://doi.org/10.1124/mol.53.3.524
Ming-Ming Zhao
Department of Molecular Cardiology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert J. Gaivin
Department of Molecular Cardiology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dianne M. Perez
Department of Molecular Cardiology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195
  • 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

Chimeric receptors of the β2-adrenergic receptor in which the extracellular loops were replaced with the corresponding amino acids of the α1a-adrenergic receptor were generated to measure changes in α1-antagonist affinity. Although no changes in α1-antagonist affinity were measured in the β2/α1a chimeras, a decreased IC50 (10-fold) for agonists as compared with wild type β2 control was found because of the replacement of the third extracellular loop (EX3). These agonist high affinity changes were because of a greater proportion of high affinity sites (2-fold) that were convertible to low affinity sites with guanosine 5′-3-O-(thio)triphosphate. Adenylate cyclase activity evoked by the EX3 chimera showed commensurate increases in the basal signal transduction as well as the isoproterenol-stimulated potency, suggesting constitutive activity. However, unlike other constitutively active adrenergic receptor mutants in which the mutation causes G protein-independent changes, the mechanism of the EX3 chimera seems to be attributable to a greater ease with which the active ternary complex is formed because of a higher affinity/coupling of the G protein. Although the changes because of EX3 are indirect and most likely affect helical packing, they support an emerging hypothesis that G protein-coupled receptors have evolved their structure-function relationships to constrain the receptor in an inactive state.

Footnotes

    • Received August 19, 1997.
    • Accepted November 21, 1997.
  • Send reprint requests to: Dr. Dianne M. Perez, Department of Molecular Cardiology, FF3-01, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, Ohio 44195. E-mail:perezd{at}cesmtp.ccf.org

  • ↵1 Current affiliation: Division of Hematology, Vanderbilt University, Nashville, TN 37232.

  • This work was supported in part by National Institutes of Health Grant RO1-HL52544 (D.M.P.) and an unrestricted research grant from Glaxo Wellcome. This work was done under the tenure of an Established Investigator Award from the American Heart Association (D.M.P.).

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

Log in using your username and password

Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

PreviousNext
Back to top

In this issue

Molecular Pharmacology: 53 (3)
Molecular Pharmacology
Vol. 53, Issue 3
1 Mar 1998
  • 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.
The Third Extracellular Loop of the β2-Adrenergic Receptor Can Modulate Receptor/G Protein Affinity
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
Citation Tools
Research ArticleArticle

The Third Extracellular Loop of the β2-Adrenergic Receptor Can Modulate Receptor/G Protein Affinity

Ming-Ming Zhao, Robert J. Gaivin and Dianne M. Perez
Molecular Pharmacology March 1, 1998, 53 (3) 524-529; DOI: https://doi.org/10.1124/mol.53.3.524

Citation Manager Formats

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

The Third Extracellular Loop of the β2-Adrenergic Receptor Can Modulate Receptor/G Protein Affinity

Ming-Ming Zhao, Robert J. Gaivin and Dianne M. Perez
Molecular Pharmacology March 1, 1998, 53 (3) 524-529; DOI: https://doi.org/10.1124/mol.53.3.524
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
    • Experimental Procedures
    • Results and Discussion
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • BODIPY-cyclopamine Binding to Nluc-SMO
  • Operational Models for Receptors with Multiple Agonist Sites
  • Characterization and optimization of the novel TRPM2 antagonist tatM2NX
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 © 2019 by the American Society for Pharmacology and Experimental Therapeutics