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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleNEUROPHARMACOLOGY

Chronic Morphine-Induced Changes in μ-Opioid Receptors and G Proteins of Different Subcellular Loci in Rat Brain

G. Fábián, B. Bozó, M. Szikszay, G. Horváth, C. J. Coscia and M. Szücs
Journal of Pharmacology and Experimental Therapeutics August 2002, 302 (2) 774-780; DOI: https://doi.org/10.1124/jpet.102.036152
G. Fábián
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B. Bozó
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Szikszay
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G. Horváth
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. J. Coscia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Szücs
  • 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

Prolonged exposure to opioid agonists can induce adaptive changes resulting in tolerance and dependence. Here, rats were rendered tolerant by subcutaneous injections of increasing doses of morphine from 10 to 60 mg/kg for 3, 5, or 10 consecutive days. Binding parameters of the μ-opioid receptor in subcellular fractions were measured with [3H]DAMGO ([d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin). Although the density of surface μ-sites did not change after the 5-day morphine treatment, up-regulation of synaptic plasma membrane binding was detected after the 10-day drug administration. In contrast, the number of μ-binding sites in a light vesicle or microsomal fraction (MI) was elevated by 68 and 30% after 5 and 10 days of morphine exposure, respectively. The up-regulated MI μ-sites displayed enhanced coupling to G proteins compared with those detected in saline-treated controls. Pertussis toxin catalyzed ADP ribosylation, and Western blotting with specific antisera was used to quantitate chronic morphine-induced changes in levels of various G protein α-subunits. Morphine treatment of 5 days and longer induced significant increases in levels of Gαo, Gαi1, and Gαi2 in MI fractions that are part of an adaptation process. Up-regulation of intracellular μ-sites may be the result of post-translational changes and in part de novo synthesis. The results provide the first evidence that distinct regulation of intracellular μ-opioid receptor G protein coupling and G protein levels may accompany the development of morphine tolerance.

Footnotes

  • This work was supported by the United States-Hungarian Science and Technology Joint Fund under Project JFNo-564, and the Hungarian Research Fund OTKA T-16084, T-33062. B.B. was a fellow of the Ph.D. program of Albert Szent-Györgyi Medical University (Szeged, Hungary).

  • DOI: 10.1124/jpet.102.036152

  • Abbreviations:
    SPM
    synaptic plasma membrane
    MI
    microsomal fraction
    DAMGO
    [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin
    [35S]GTPγS
    guanosine 5′-O-(3-[35S]thio)triphosphate
    PTX
    pertussis toxin
    PAGE
    polyacrylamide gel electrophoresis
    • Received March 14, 2002.
    • Accepted April 25, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 302 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 302, Issue 2
1 Aug 2002
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics 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 Morphine-Induced Changes in μ-Opioid Receptors and G Proteins of Different Subcellular Loci in Rat Brain
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleNEUROPHARMACOLOGY

Chronic Morphine-Induced Changes in μ-Opioid Receptors and G Proteins of Different Subcellular Loci in Rat Brain

G. Fábián, B. Bozó, M. Szikszay, G. Horváth, C. J. Coscia and M. Szücs
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 774-780; DOI: https://doi.org/10.1124/jpet.102.036152

Citation Manager Formats

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

Share
Research ArticleNEUROPHARMACOLOGY

Chronic Morphine-Induced Changes in μ-Opioid Receptors and G Proteins of Different Subcellular Loci in Rat Brain

G. Fábián, B. Bozó, M. Szikszay, G. Horváth, C. J. Coscia and M. Szücs
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 774-780; DOI: https://doi.org/10.1124/jpet.102.036152
del.icio.us logo Digg logo Reddit logo Twitter 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
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Iclepertin (BI 425809) in schizophrenia-related models
  • D1 agonist vs. methylphenidate on PFC working memory
  • Obesity Thwarts Preconditioning in TBI
Show more Neuropharmacology

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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics