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

α2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

Carolyn A. Fairbanks, Laura S. Stone, Kelley F. Kitto, H. Oanh Nguyen, Ivan J. Posthumus and George L. Wilcox
Journal of Pharmacology and Experimental Therapeutics January 2002, 300 (1) 282-290; DOI: https://doi.org/10.1124/jpet.300.1.282
Carolyn A. Fairbanks
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura S. Stone
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kelley F. Kitto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H. Oanh Nguyen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ivan J. Posthumus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
George L. Wilcox
  • 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 α2A-adrenergic receptor (AR) subtype mediates antinociception induced by the α2AR agonists clonidine, dexmedetomidine, norepinephrine, and 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK-14,304) as well as antinociceptive synergy of UK-14,304 with opioid agonists [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin and deltorphin II. Differential localization of α2-adrenergic (α2A-, α2B-, α2C-) and opioid (μ-, δ-, κ-) subtypes suggests differential involvement of subtype pairs in opioid-adrenergic analgesic synergy. The present study applies a novel imidazoline1/α2-adrenergic receptor analgesic, moxonidine, to test for involvement of α2B- and α2CARs in antinociception and antinociceptive synergy, because spinal antinociceptive activity of moxonidine shows minimal dependence on α2AAR. Intrathecal administration of moxonidine produced similar (2–3-fold) decreases in both mutant mice with a functional knockout of α2AAR (D79N-α2AAR) and α2CAR knockout (KO) mice. The potency of moxonidine was not altered in α2BKO mice, indicating that this subtype does not participate in moxonidine-induced spinal antinociception. Moxonidine-mediated antinociception was dose dependently inhibited by the selective α2-receptor antagonist SK&F 86466 in both D79N-α2A mice and α2CKO mice, indicating that α2AR activation is required in the absence of either α2A- or α2CAR. Spinal administration of antisense oligodeoxynucleotides directed against the α2CAR decreased both α2CAR immunoreactivity and the antinociceptive potency of moxonidine. Isobolographic analysis demonstrates that moxonidine-deltorphin antinociceptive synergy is present in the D79N-α2A mice but not in the α2CAR-KO mice. These results confirm that the α2CAR subtype contributes to spinal antinociception and synergy with opioids.

Footnotes

  • This study was supported by National Institutes of Health Grants R01-DA-01933 and R01-DA-11236 to G.L.W. National Institute on Drug Abuse training Grant T32A07234 supported C.A.F.

  • Abbreviations

    AR
    adrenergic receptor
    KO
    knockout
    OE
    over-expresser
    WT
    wild-type
    SP
    substance P
    ODN
    oligodeoxynucleotide
    CL
    confidence limits
    I1 imidazoline1
    -ir, immunoreactivity
    DRG
    dorsal root ganglion
    UK-14,304
    5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine
    • Received June 19, 2001.
    • Accepted September 12, 2001.
    • 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: 300 (1)
    Journal of Pharmacology and Experimental Therapeutics
    Vol. 300, Issue 1
    1 Jan 2002
    • 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 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.
    α2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy
    (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

    α2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

    Carolyn A. Fairbanks, Laura S. Stone, Kelley F. Kitto, H. Oanh Nguyen, Ivan J. Posthumus and George L. Wilcox
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 282-290; DOI: https://doi.org/10.1124/jpet.300.1.282

    Citation Manager Formats

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

    Share
    Research ArticleNEUROPHARMACOLOGY

    α2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

    Carolyn A. Fairbanks, Laura S. Stone, Kelley F. Kitto, H. Oanh Nguyen, Ivan J. Posthumus and George L. Wilcox
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 282-290; DOI: https://doi.org/10.1124/jpet.300.1.282
    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
      • Materials and Methods
      • Results
      • Discussion
      • Acknowledgments
      • Footnotes
      • Abbreviations
      • References
    • Figures & Data
    • Info & Metrics
    • eLetters
    • PDF

    Related Articles

    Cited By...

    More in this TOC Section

    • D1 agonist vs. methylphenidate on PFC working memory
    • Iclepertin (BI 425809) in schizophrenia-related models
    • 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