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
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
    • 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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Incorporation of the π Subunit into Functional γ-Aminobutyric AcidA Receptors

Torben R. Neelands and Robert L. Macdonald
Molecular Pharmacology September 1999, 56 (3) 598-610; DOI: https://doi.org/10.1124/mol.56.3.598
Torben R. Neelands
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert L. Macdonald
1 2 3
  • 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

mRNA encoding the recently cloned γ-aminobuytyric acidAreceptor (GABAR) π subunit is expressed in the hippocampus and in several non-neuronal tissues including the uterus and ovaries. Whereas native GABARs are pentamers composed primarily of αβγ, αβδ, or αβε subunits, it has not been demonstrated clearly that the π subunit incorporates into functional GABARs to form αβπ receptors and, if so, with what properties. We provide electrophysiological evidence that the π subunit can coassemble with either α5β3 or α5β3γ3 subunits to produce recombinant GABARs with distinct pharmacological and biophysical properties. Compared with α5β3 receptors, GABARs produced by coexpression of α5β3π subunits had a lower GABA EC50 value, were enhanced to a lesser extent by loreclezole, had different IC50 values for pregnenolone sulfate and lanthanum, and were insensitive to benzodiazepines. Incorporation of both π and γ3 subunits into an α5β3γ3π isoform was suggested by reduced enhancement by diazepam and a high zinc IC50 value. Current-voltage relations for the α5β3π subunit combination outwardly rectified more than currents from α5β3γ3 but less than α5β3 combination GABARs. Single-channel α5β3 GABAR currents had a main conductance state of 15.2 picoSeimens (pS). Coexpression of the π subunit with α5β3 subtypes increased the conductance level to 23.8 pS, similar to the conductance level of α5β3γ3 GABARs (26.9 pS). We conclude that the π subunit coassembles with α, β, and γ subunits to form functional αβπ or αβγπ GABARs and, thus, could have a significant impact on the function of native GABARs expressed in the brain or non-neuronal tissue.

Footnotes

    • Received January 19, 1999.
    • Accepted May 21, 1999.
  • Send reprint requests to: Robert L. Macdonald, M.D., Ph.D., Neuroscience Laboratory Building, University of Michigan Medical School, 1103 East Huron St., Ann Arbor, MI 48104-1687. E-mail:rlmacd{at}umich.edu

  • ↵1 Current address: Bollum Institute, Oregon Health Sciences University, Portland, OR 97201.

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 56 (3)
Molecular Pharmacology
Vol. 56, Issue 3
1 Sep 1999
  • 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.
Incorporation of the π Subunit into Functional γ-Aminobutyric AcidA Receptors
(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

Incorporation of the π Subunit into Functional γ-Aminobutyric AcidA Receptors

Torben R. Neelands and Robert L. Macdonald
Molecular Pharmacology September 1, 1999, 56 (3) 598-610; DOI: https://doi.org/10.1124/mol.56.3.598

Citation Manager Formats

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

Share
Research ArticleArticle

Incorporation of the π Subunit into Functional γ-Aminobutyric AcidA Receptors

Torben R. Neelands and Robert L. Macdonald
Molecular Pharmacology September 1, 1999, 56 (3) 598-610; DOI: https://doi.org/10.1124/mol.56.3.598
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Antimicrobial and Antileukemic Transportan 10 Conjugates
  • Pharmacological characterization of zebrafish H1 receptor
  • Bhave and Forman
Show more Article

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 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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics