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

M2, M3, and M4 Receptor Subtypes Contribute to Muscarinic Potentiation of GABAergic Inputs to Spinal Dorsal Horn Neurons

Hong-Mei Zhang, De-Pei Li, Shao-Rui Chen and Hui-Lin Pan
Journal of Pharmacology and Experimental Therapeutics May 2005, 313 (2) 697-704; DOI: https://doi.org/10.1124/jpet.104.079939
Hong-Mei Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
De-Pei Li
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shao-Rui Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hui-Lin Pan
  • 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 spinal cholinergic system and muscarinic receptors are important for regulation of nociception. Activation of spinal muscarinic receptors produces analgesia and inhibits dorsal horn neurons through potentiation of GABAergic inputs. To determine the role of receptor subtypes in the muscarinic agonist-induced synaptic GABA release, spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded in lamina II neurons using whole-cell voltage-clamp recordings in rat spinal cord slices. The muscarinic receptor agonist oxotremorine-M dose-dependently (1–10 μM) increased GABAergic sIPSCs but not miniature IPSCs. The potentiating effect of oxotremorine-M on sIPSCs was completely blocked by atropine. In rats pretreated with intrathecal pertussis toxin to inactive inhibitory G i/o proteins, 3 μM oxotremorine-M had no significant effect on sIPSCs in 31 of 55 (56%) neurons tested. In the remaining 24 (44%) neurons in pertussis toxin-treated rats, oxotremorine-M caused a small increase in sIPSCs, and this effect was completely abolished by subsequent application of 25 nM 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), a relatively selective M3 subtype antagonist. Furthermore, himbacine (1 μM), a relatively specific antagonist for M2 and M4 subtypes, produced a large reduction in the stimulatory effect of oxotremorine-M on sIPSCs, and the remaining effect was abolished by 4-DAMP. Additionally, the M4 receptor antagonist MT-3 toxin (100 nM) significantly attenuated the effect of oxotremorine-M on sIPSCs. Collectively, these data suggest that M2 and M4 receptor subtypes play a predominant role in muscarinic potentiation of synaptic GABA release in the spinal cord. The M3 subtype also contributes to increased GABAergic tone in spinal dorsal horn by muscarinic agonists.

Footnotes

  • This study was supported by Grants GM64830 and NS45602 from the National Institutes of Health.

  • doi:10.1124/jpet.104.079939.

  • ABBREVIATIONS: PTX, pertussis toxin; aCSF, artificial cerebrospinal fluid; QX314, lidocaine N-ethyl bromide; GDP-β-S, guanosine 5′-O-(2-thiodiphosphate); sIPSC, spontaneous inhibitory postsynaptic current; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; mIPSC, miniature inhibitory postsynaptic current; TTX, tetrodotoxin; 4-DAMP, 4-diphenylacetoxy-N-methylpiperidine methiodide; CGP55845, (3-N-[1-(5)-3,4-dichlorophenyl)-ethyl]-amino-2-(s)-hydroxypropyl)-benzyl-phosphinic acid.

    • Received November 1, 2004.
    • Accepted January 5, 2005.
  • 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.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 376 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 376, Issue 2
1 Feb 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
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.
M2, M3, and M4 Receptor Subtypes Contribute to Muscarinic Potentiation of GABAergic Inputs to Spinal Dorsal Horn Neurons
(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

M2, M3, and M4 Receptor Subtypes Contribute to Muscarinic Potentiation of GABAergic Inputs to Spinal Dorsal Horn Neurons

Hong-Mei Zhang, De-Pei Li, Shao-Rui Chen and Hui-Lin Pan
Journal of Pharmacology and Experimental Therapeutics May 1, 2005, 313 (2) 697-704; DOI: https://doi.org/10.1124/jpet.104.079939

Citation Manager Formats

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

M2, M3, and M4 Receptor Subtypes Contribute to Muscarinic Potentiation of GABAergic Inputs to Spinal Dorsal Horn Neurons

Hong-Mei Zhang, De-Pei Li, Shao-Rui Chen and Hui-Lin Pan
Journal of Pharmacology and Experimental Therapeutics May 1, 2005, 313 (2) 697-704; DOI: https://doi.org/10.1124/jpet.104.079939
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
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Pharmacology of Carbamate Insecticides at Melatonin Receptors
  • Metalloporphyrins modify disease outcomes in parkinsonism
  • Oxysterols and ethanol
Show more Neuropharmacology

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 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics