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

Chronic Morphine Augments Gβγ/GsαStimulation of Adenylyl Cyclase: Relevance to Opioid Tolerance

Sumita Chakrabarti, Mildred Rivera, Shui-Zhong Yan, Wei-Jen Tang and Alan R. Gintzler
Molecular Pharmacology October 1998, 54 (4) 655-662;
Sumita Chakrabarti
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mildred Rivera
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shui-Zhong Yan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei-Jen Tang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan R. Gintzler
  • 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 the current study, we investigated the neurochemical basis for the previously reported predominance of stimulatory μ-opioid signaling in guinea pig longitudinal muscle/myenteric plexus (LMMP) preparations after chronic in vivo morphine exposure. As expected, recombinant Gsα (rGsα) dose-dependently stimulated adenylyl cyclase (AC) activity in LMMP membranes obtained from opioid naive as well as tolerant LMMP tissue. However, the magnitude of the increase was significantly greater in the latter than in the former. The Gβγ blocking peptide QEHA (50 μm) essentially abolished stimulation by rGsα in LMMP membranes obtained from both opioid naive and tolerant animals. Interestingly, after partial blockade by lower QEHA concentrations, the incremental AC stimulation by rGsα in tolerant LMMP membranes was no longer observed, indicating augmented Gβγ stimulatory responsiveness. Concomitant changes in the content of AC isoform protein are consistent with these biochemical observations. After chronic systemic morphine, AC protein is augmented significantly (56%). This increment is most likely to be composed of AC isoforms that are stimulated by Gβγ. This is the first demonstration in a complex mammalian tissue that persistent activation of opioid receptors results in augmented Gβγ/Gsα AC stimulatory interactiveness. The relevance of such changes to the manifestation of opioid tolerance is discussed.

Footnotes

  • Send reprint requests to: Dr. Alan Gintzler, Box 8, Department of Biochemistry, SUNY HSCB, 450 Clarkson Avenue, Brooklyn, NY 11203.

  • ↵1 Current affiliation: United States Department of Agriculture, ARS, NPA, Roman L. Hruska U.S. Meat Animal Research Center, Clay Center, Nebraska 68933.

  • This work was supported in part by Aaron Diamond Foundation Grant HRI 817–533 (M.R., A.R.G.) and National Institutes of Health Grant GM53459 (W.J.T). M.R. was an Aaron Diamond Foundation Postdoctoral Fellow. S.C., M.R., and S.-Z.Y contributed equally to this article.

  • Abbreviations:
    AC
    adenylyl cyclase
    LMMP
    longitudinal muscle/myenteric plexus
    EGTA
    ethylene glycol bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid
    HEPES
    4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
    SDS
    sodium dodecyl sulfate
    TCA
    trichloroacetic acid
    GTPγS
    guanosine-5′-O-(3-thio)triphosphate
    DTT
    dithiothreitol
    BSA
    bovine serum albumin
    SSC
    standard saline citrate
    TES
    N-Tris[hydroxymethyl] methyl-2-aminoethane sulfonic acid
    rGsα
    recombinant Gsα
    • Received April 17, 1998.
    • Accepted July 13, 1998.
  • 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: 54 (4)
Molecular Pharmacology
Vol. 54, Issue 4
1 Oct 1998
  • 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.
Chronic Morphine Augments Gβγ/GsαStimulation of Adenylyl Cyclase: Relevance to Opioid Tolerance
(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

Chronic Morphine Augments Gβγ/GsαStimulation of Adenylyl Cyclase: Relevance to Opioid Tolerance

Sumita Chakrabarti, Mildred Rivera, Shui-Zhong Yan, Wei-Jen Tang and Alan R. Gintzler
Molecular Pharmacology October 1, 1998, 54 (4) 655-662;

Citation Manager Formats

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

Chronic Morphine Augments Gβγ/GsαStimulation of Adenylyl Cyclase: Relevance to Opioid Tolerance

Sumita Chakrabarti, Mildred Rivera, Shui-Zhong Yan, Wei-Jen Tang and Alan R. Gintzler
Molecular Pharmacology October 1, 1998, 54 (4) 655-662;
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
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of Celecoxib targets by label-free TPP
  • Editing TOP2α Intron 19 5′ SS Circumvents Drug Resistance
  • CTS Bias
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