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
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
    • 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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCellular and Molecular

Activated G Protein αs Subunits Increase the Ethanol Sensitivity of Human Glycine Receptors

Gonzalo E. Yévenes, Gustavo Moraga-Cid, Ximena Romo and Luis G. Aguayo
Journal of Pharmacology and Experimental Therapeutics November 2011, 339 (2) 386-393; DOI: https://doi.org/10.1124/jpet.111.184408
Gonzalo E. Yévenes
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gustavo Moraga-Cid
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ximena Romo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luis G. Aguayo
  • 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

It is well known that ethanol modulates the function of the Cys loop ligand-gated ion channels, which include the inhibitory glycine receptors (GlyRs). Previous studies have consistently shown that transmembrane and extracellular sites are essential for ethanol actions in GlyRs. In addition, recent evidence has shown that the ethanol modulation of GlyRs is also affected by G protein activation through Gβγ subunits. However, more specific roles of G protein α subunits on ethanol actions are unknown. Here, we show that the allosteric effect of ethanol on the human α1 GlyR is selectively enhanced by the expression of Gαs Q-L. For example, constitutively active Gαs, but not Gαq or Gαi, was able to displace the alcohol sensitivity of GlyRs toward low millimolar concentrations (17 ± 4 versus 48 ± 5% at 100 mM). Experiments under conditions that increased cAMP and protein kinase A (PKA)-mediated signaling, on the contrary, did not produce the same enhancement in sensitivity, suggesting that the Gαs Q-L effect was not dependent on cAMP/PKA-dependent signaling. On the other hand, the effect of Gαs Q-L was blocked by a Gβγ scavenger (9 ± 3% of control). Furthermore, two mutant receptors previously shown to have impaired interactions with Gβγ were not affected by Gαs Q-L, suggesting that Gβγ is needed for enhancing ethanol sensitivity. These results support the conclusion that activated Gαs can facilitate the Gβγ interaction with GlyRs in presence of ethanol, independent of increases in cAMP signaling. Thus, these data indicate that the activated form of Gαs is able to positively influence the effect of ethanol on a type of inhibitory receptor important for motor control, pain, and respiration.

Footnotes

  • This work was supported by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant AA15150]; and Comisión Nacional de Investigación Científica y Tecnológica [Grant AT-4040102].

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

    doi:10.1124/jpet.111.184408.

  • ABBREVIATIONS:

    LGIC
    ligand-gated ion channel
    GABAAR
    GABA receptor
    GlyR
    glycine receptor
    TM
    transmembrane
    GPCR
    G protein-coupled receptor
    BAPTA
    1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid
    PKA
    protein kinase A
    HEK
    human embryonic kidney
    GFP
    green fluorescent protein
    ANOVA
    analysis of variance
    ct-GRK
    carboxyl-terminal G protein-coupled receptor kinase.

  • Received June 6, 2011.
  • Accepted August 4, 2011.
  • Copyright © 2011 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: 339 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 339, Issue 2
1 Nov 2011
  • 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 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.
Activated G Protein αs Subunits Increase the Ethanol Sensitivity of Human Glycine 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 ArticleCellular and Molecular

Gαs Increases the Ethanol Potentiation of Glycine Receptors

Gonzalo E. Yévenes, Gustavo Moraga-Cid, Ximena Romo and Luis G. Aguayo
Journal of Pharmacology and Experimental Therapeutics November 1, 2011, 339 (2) 386-393; DOI: https://doi.org/10.1124/jpet.111.184408

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

Gαs Increases the Ethanol Potentiation of Glycine Receptors

Gonzalo E. Yévenes, Gustavo Moraga-Cid, Ximena Romo and Luis G. Aguayo
Journal of Pharmacology and Experimental Therapeutics November 1, 2011, 339 (2) 386-393; DOI: https://doi.org/10.1124/jpet.111.184408
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PARPi with vitamin C, decitabine or azacitidine for APL.
  • Circ-KRT6C/miR-485-3p/PDL1 axis in colorectal cancer.
  • Zebrafish Gstp1 Drug Response
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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics