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

Contrasting Modes of Action of Methylglutamate Derivatives on the Excitatory Amino Acid Transporters, EAAT1 and EAAT2

Robert J. Vandenberg, Ann D. Mitrovic, Mary Chebib, Vladimir J. Balcar and Graham A. R. Johnston
Molecular Pharmacology May 1997, 51 (5) 809-815; DOI: https://doi.org/10.1124/mol.51.5.809
Robert J. Vandenberg
Departments of 1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ann D. Mitrovic
Departments of 1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mary Chebib
Departments of 1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vladimir J. Balcar
Departments of 1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Graham A. R. Johnston
Departments of 1 2
  • 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

We have investigated the mechanism of action of a series of glutamate derivatives on the cloned excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2), expressed in Xenopus laevis oocytes. The compounds were tested as substrates and competitive blockers of the glutamate transporters. A number of compounds showed contrasting mechanisms of action on EAAT1 compared with EAAT2. In particular, (2S,4R)-4-methylglutamate and 4-methylene-glutamate were transported by EAAT1, withK m values of 54 μm and 391 μm, respectively, but potently blocked glutamate transport by EAAT2, withK b values of 3.4 μm and 39 μm, respectively. Indeed, (2S,4R)-4-methylglutamate is the most potent blocker of EAAT2 yet described. (±)-Threo-3-methylglutamate also potently blocked glutamate transport by EAAT2 (K b = 18 μm), but was inactive on EAAT1 as either a substrate or a blocker at concentrations up to 300 μm. In contrast to (2S,4R)-4-methylglutamate,l-threo-4-hydroxyglutamate was a substrate for both EAAT1 and EAAT2, with K m values of 61 μm and 48 μm, respectively. It seems that the chemical nature and also the orientation of the group at the 4-position of the carbon backbone of glutamate is crucial in determining the pharmacological activity. The conformations of these molecules have been modeled to understand the structural differences between, firstly, compounds that are blockers versus substrates of EAAT2 and, secondly, the pharmacological differences between EAAT1 and EAAT2.

Footnotes

    • Received November 25, 1996.
    • Accepted January 22, 1997.
  • Send reprint requests to: Dr. Robert Vandenberg, Department of Pharmacology, D06, University of Sydney, Sydney, New South Wales, 2006, Australia. E-mail:robv{at}pharmacol.su.oz.au

  • This study was supported by the Australian National Health and Medical Research Council and the Ramaciotti Foundation.

  • 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: 51 (5)
Molecular Pharmacology
Vol. 51, Issue 5
1 May 1997
  • 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.
Contrasting Modes of Action of Methylglutamate Derivatives on the Excitatory Amino Acid Transporters, EAAT1 and EAAT2
(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

Contrasting Modes of Action of Methylglutamate Derivatives on the Excitatory Amino Acid Transporters, EAAT1 and EAAT2

Robert J. Vandenberg, Ann D. Mitrovic, Mary Chebib, Vladimir J. Balcar and Graham A. R. Johnston
Molecular Pharmacology May 1, 1997, 51 (5) 809-815; DOI: https://doi.org/10.1124/mol.51.5.809

Citation Manager Formats

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

Share
Research ArticleArticle

Contrasting Modes of Action of Methylglutamate Derivatives on the Excitatory Amino Acid Transporters, EAAT1 and EAAT2

Robert J. Vandenberg, Ann D. Mitrovic, Mary Chebib, Vladimir J. Balcar and Graham A. R. Johnston
Molecular Pharmacology May 1, 1997, 51 (5) 809-815; DOI: https://doi.org/10.1124/mol.51.5.809
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
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Analgesic Effects and Mechanisms of Licochalcones
  • Induced Fit Ligand Binding to CYP3A4
  • Englerin A Inhibits T-Type Channels
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