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
Abstract

Chronic benzodiazepine agonist treatment produces functional uncoupling of the gamma-aminobutyric acid-benzodiazepine receptor ionophore complex in cortical neurons.

X J Hu and M K Ticku
Molecular Pharmacology April 1994, 45 (4) 618-625;
X J Hu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M K Ticku
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

We have investigated the effect of chronic flurazepam HCl treatment on the gamma-aminobutyric acid (GABA)A receptor complex in cultured mammalian cortical neurons. Chronic flurazepam (1-5 microM, for 1-10 days) treatment did not produce any changes in the morphological appearance or the cell protein content of cortical neurons. The basal binding of [3H]flunitrazepam, [3H] Ro15-1788, and [3H]Ro15-4513 was also not altered after the chronic treatment. However, chronic flurazepam treatment produced uncoupling between GABA and pentobarbital sites and the [3H]flunitrazepam binding site. The EC50 values of GABA and pentobarbital were not significantly altered after chronic flurazepam treatment; however, their Emax values were decreased by approximately 50%. The effect of chronic flurazepam treatment on the observed uncoupling was both time and concentration dependent. Furthermore, the binding of [3H]GABA and t-butylbicyclophosphoro[35S]thionate was also not altered by chronic flurazepam treatment. The effect of GABA on 36Cl influx was not altered after chronic flurazepam treatment; however, treatment significantly attenuated the ability of diazepam to enhance GABA-induced 36Cl influx. Chronic flurazepam-induced uncoupling and decreased diazepam efficacy were reversed by the concomitant presence of the benzodiazepine antagonist Ro15-1788, suggesting that these events are mediated via the benzodiazepine receptor site. Taken together, these results suggest that chronic benzodiazepine treatment produces uncoupling of GABA and pentobarbital sites from the benzodiazepine site and decreased coupling between the benzodiazepine site and GABA receptor-gated Cl- channels. The uncoupling and decreased efficacy may be due to an alteration in the levels of various alpha subunits and may be responsible for the tolerance associated with chronic benzodiazepine agonist treatment.

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
Vol. 45, Issue 4
1 Apr 1994
  • Table of Contents
  • Table of Contents (PDF)
  • 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 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.
Chronic benzodiazepine agonist treatment produces functional uncoupling of the gamma-aminobutyric acid-benzodiazepine receptor ionophore complex in cortical neurons.
(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
Abstract

Chronic benzodiazepine agonist treatment produces functional uncoupling of the gamma-aminobutyric acid-benzodiazepine receptor ionophore complex in cortical neurons.

X J Hu and M K Ticku
Molecular Pharmacology April 1, 1994, 45 (4) 618-625;

Citation Manager Formats

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

Share
Abstract

Chronic benzodiazepine agonist treatment produces functional uncoupling of the gamma-aminobutyric acid-benzodiazepine receptor ionophore complex in cortical neurons.

X J Hu and M K Ticku
Molecular Pharmacology April 1, 1994, 45 (4) 618-625;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

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