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 ArticleCELLULAR AND MOLECULAR

Monovalent Anions Differentially Modulate Coupling of the β2-Adrenoceptor to Gsα Splice Variants

Roland Seifert
Journal of Pharmacology and Experimental Therapeutics August 2001, 298 (2) 840-847;
Roland Seifert
  • 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 β2-adrenoceptor (β2AR) fused to the long splice variant of Gsα(GsαL), but not the β2AR fused to the short splice variant of Gsα(GsαS) shows the hallmarks of high constitutive activity, i.e., strong activation of adenylyl cyclase (AC) by GTP and strong inhibition of AC by inverse agonist. These coupling differences are the result of differences in GDP affinity of Gsα splice variants. The aim of this study was to identify experimental variables that differentially affect β2AR coupling to GsαS and GsαL. NaCl substantially reduced agonist-independent AC activation by GTP and inverse agonist inhibition and enhanced agonist stimulation of AC in Sf9 insect cell membranes expressing the β2AR-GsαL fusion protein. Salts reduced inverse agonist inhibition and increased agonist stimulation of AC in the order of efficiency NaI ∼ KI > NaBr ∼ KBr > NaCl ∼ LiCl ∼ KCl ∼ RbCl ∼ CsCl ∼ choline chloride, indicating that monovalent anions determine salt effects. Salts inhibited guanosine 5′-O-(3-thiotriphosphate)-mediated AC activation by GsαL without β2AR in the order of efficiency NaI > NaBr > NaCl. NaCl enhanced the affinity of GsαL for GDP. Salts had much smaller effects on β2AR ligand regulation of AC in membranes expressing β2AR-GsαS than in membranes expressing β2AR-GsαL. These data are explained by a model in which anions increase the GDP affinity of GsαL more efficiently than the GDP affinity of GsαS, and, thereby, decrease the efficiency of the agonist-free β2AR and increase the efficiency of the agonist-occupied β2AR at promoting GDP dissociation from GsαL. Thus, monovalent anions differentially regulate β2AR-coupling to GsαS and GsαL.

Footnotes

  • The J. R. & Inez Jay Biomedical Research Award, a New Faculty Award of The University of Kansas, and a grant of the Army Research Office (DAAD19-00-1-0069) to R. S. supported this project. Initial experiments for this project were carried out at the Howard Hughes Medical Institute, Stanford University, Beckman Center, Stanford, CA 94305.

  • Abbreviations:
    β2AR
    β2-adrenoceptor
    GPCR
    G protein-coupled receptor
    Gs protein
    G protein activating adenylyl cyclase
    AC
    adenylyl cyclase
    Gα
    nonspecified G protein α-subunit
    GsαL
    long splice variant of the Gs protein Gsα
    GsαS
    short splice variant of the Gs protein Gsα
    β2AR-GsαL
    fusion protein containing the β2AR and the long splice variant of Gsα
    β2AR-GsαS
    fusion protein containing the β2AR and the short splice variant of Gsα
    Gi protein
    G protein inhibiting adenylyl cyclase
    Go protein
    G protein expressed at high levels in the brain and neuroendocrine cells
    DHA
    [3H]dihydroalprenolol
    ICI
    ICI 118,551 [erythro-d-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol]
    ISO
    (−)-isoproterenol
    ChoCl
    choline chloride
    GTPγS
    guanosine 5′-O-(3-thio)triphosphate
    • Received December 12, 2000.
    • Accepted April 16, 2001.
  • 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: 298 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 2
1 Aug 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 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.
Monovalent Anions Differentially Modulate Coupling of the β2-Adrenoceptor to Gsα Splice Variants
(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 ArticleCELLULAR AND MOLECULAR

Monovalent Anions Differentially Modulate Coupling of the β2-Adrenoceptor to Gsα Splice Variants

Roland Seifert
Journal of Pharmacology and Experimental Therapeutics August 1, 2001, 298 (2) 840-847;

Citation Manager Formats

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

Share
Research ArticleCELLULAR AND MOLECULAR

Monovalent Anions Differentially Modulate Coupling of the β2-Adrenoceptor to Gsα Splice Variants

Roland Seifert
Journal of Pharmacology and Experimental Therapeutics August 1, 2001, 298 (2) 840-847;
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
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CsA downregulates Selenop expression via a STAT3-FoxO1 axis
  • Anisodamine Ameliorates Acute Lung Injury
  • ACE2 Inhibits LPS-Caused Lung Fibrosis
Show more Cellular and Molecular

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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics