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

Inverse Agonist Properties of Dopaminergic Antagonists at the D1A Dopamine Receptor: Uncoupling of the D1ADopamine Receptor from Gs Protein

Guoping Cai, Hakan Gurdal, Candyce Smith, Hoau-Yan Wang and Eitan Friedman
Molecular Pharmacology November 1999, 56 (5) 989-996; DOI: https://doi.org/10.1124/mol.56.5.989
Guoping Cai
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hakan Gurdal
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Candyce Smith
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hoau-Yan Wang
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eitan Friedman
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

The interaction of dopaminergic antagonists with the D1Adopamine receptor was assessed in PC2 cells that transiently express this receptor. The maximal binding and dissociation constants for the D1A dopamine receptor, using the ligand [125I]SCH23982 were 0.38 ± 0.09 nM and 1 to 4 pmol/mg, respectively, when assessed 48 h after transfection with cDNA encoding the rat D1A receptor. Basal adenylyl cyclase activity increased 50 to 60% in membranes of transfected PC2 cells compared with control membranes. The dopaminergic antagonists clozapine, cis-flupenthixol, (+)-butaclamol, haloperidol, chlorpromazine, and fluphenazine inhibited constitutive adenylyl cyclase activity in membranes of cells expressing the D1A receptor. SCH23390, a selective D1 dopamine receptor antagonist, and (−)-butaclamol did not alter basal cyclase activity, whereas dopamine increased enzyme activity in membranes expressing the D1A dopamine receptor. The coupling of D1A receptors with Gs proteins was examined by immunoprecipitation of membrane Gsα followed by immunoblotting with a D1A dopamine receptor monoclonal antibody. Clozapine, cis-flupenthixol, (+)-butaclamol, haloperidol, and fluphenazine but not SCH23390 or (−)-butaclamol decreased D1A receptor-Gsα coupling by 70 to 80%, and SCH23390 was able to prevent the receptor-Gsαuncoupling induced by haloperidol or clozapine. These results indicate that some dopaminergic antagonists suppress basal signal transduction and behave as inverse agonists at the D1A dopamine receptor. This action of the dopamine receptor antagonists may contribute to their antidopaminergic properties that seem to underlie their clinical actions as antipsychotic drugs.

Footnotes

    • Received February 15, 1999.
    • Accepted August 9, 1999.
  • Send reprint requests to: Eitan Friedman, Ph.D., Department of Pharmacology, MCP Hahnemann School of Medicine, 3200 Henry Avenue, Philadelphia, PA 19129-1137. E-mail:friedmane{at}mcphu.edu

  • This study was supported by United States Public Health Service Grants NS29514, from the National Institute of Neurological Disorders and Stroke, and T32-AG00131, from the National Institute on Aging.

  • 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: 56 (5)
Molecular Pharmacology
Vol. 56, Issue 5
1 Nov 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.
Inverse Agonist Properties of Dopaminergic Antagonists at the D1A Dopamine Receptor: Uncoupling of the D1ADopamine Receptor from Gs Protein
(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

Inverse Agonist Properties of Dopaminergic Antagonists at the D1A Dopamine Receptor: Uncoupling of the D1ADopamine Receptor from Gs Protein

Guoping Cai, Hakan Gurdal, Candyce Smith, Hoau-Yan Wang and Eitan Friedman
Molecular Pharmacology November 1, 1999, 56 (5) 989-996; DOI: https://doi.org/10.1124/mol.56.5.989

Citation Manager Formats

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

Share
Research ArticleArticle

Inverse Agonist Properties of Dopaminergic Antagonists at the D1A Dopamine Receptor: Uncoupling of the D1ADopamine Receptor from Gs Protein

Guoping Cai, Hakan Gurdal, Candyce Smith, Hoau-Yan Wang and Eitan Friedman
Molecular Pharmacology November 1, 1999, 56 (5) 989-996; DOI: https://doi.org/10.1124/mol.56.5.989
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Differential Drug Effects on Homo/Heteromeric hERG Channels
  • ACKR3 Senses CXCR4 Activation Through GRK Phosphorylation
  • Analgesic Effects and Mechanisms of Licochalcones
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