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

Down-regulation of μ-Opioid Receptor by Full but Not Partial Agonists Is Independent of G Protein Coupling

Nirmala Yabaluri and Fedor Medzihradsky
Molecular Pharmacology November 1997, 52 (5) 896-902; DOI: https://doi.org/10.1124/mol.52.5.896
Nirmala Yabaluri
Departments of Biological Chemistry and Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fedor Medzihradsky
Departments of Biological Chemistry and Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109
  • 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

In C6 glial cells stably expressing rat μ-opioid receptor, opioid agonist activation is negatively coupled to adenylyl cyclase through pertussis toxin-sensitive G proteins. In membranes, [d-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAMGO) increases guanosine-5′-O-(3-[35S]thio)triphosphate (GTP[γ-35S]) binding by 367% with an EC50value of 28 nm. Prolonged exposure to agonists induced desensitization of the receptor as estimated by a reduction in the maximal stimulation of GTP[γ-35S] binding by DAMGO and rightward shifts in the dose-response curves. In cells treated with 10 μm concentrations of etorphine, DAMGO, β-endorphin, morphine, and butorphanol, DAMGO-stimulated GTP[γ-35S] binding was 58%, 149%, 205%, 286%, and 325%, respectively. Guanine nucleotide regulation of agonist binding was correspondingly lower in membranes from tolerant cells. Furthermore, chronic opioid treatment increased forskolin-stimulated adenylyl cyclase activity, and potency of DAMGO to inhibit cAMP accumulation was lower in morphine- and DAMGO-tolerant cells (EC50 = 55 and 170 nmversus 18 nm for control). Chronic treatment with agonists reduced [3H]DAMGO binding in membranes with the rank order of etorphine > DAMGO = β-endorphin > morphine > butorphanol, and the affinity of DAMGO in alkaloid- but not peptide-treated membranes was significantly lower in comparison with control. Pertussis toxin treatment of the cells before agonist treatment did not prevent the down-regulation by full agonists; DAMGO and etorphine exhibited ∼80% internalization, whereas the ability of partial agonists was greatly impaired. In addition to establishing this cell line as a good model for further studies on the mechanisms of opioid tolerance, these results indicate important differences in the inactivation pathways of receptor triggered by full and partial agonists.

  • 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: 52 (5)
Molecular Pharmacology
Vol. 52, Issue 5
1 Nov 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.
Down-regulation of μ-Opioid Receptor by Full but Not Partial Agonists Is Independent of G Protein Coupling
(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

Down-regulation of μ-Opioid Receptor by Full but Not Partial Agonists Is Independent of G Protein Coupling

Nirmala Yabaluri and Fedor Medzihradsky
Molecular Pharmacology November 1, 1997, 52 (5) 896-902; DOI: https://doi.org/10.1124/mol.52.5.896

Citation Manager Formats

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

Down-regulation of μ-Opioid Receptor by Full but Not Partial Agonists Is Independent of G Protein Coupling

Nirmala Yabaluri and Fedor Medzihradsky
Molecular Pharmacology November 1, 1997, 52 (5) 896-902; DOI: https://doi.org/10.1124/mol.52.5.896
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
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CTS bias
  • Nelfinavir and PXR
  • P2X7 Positive Modulator Structure-Activity Relationship
Show more Article

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics