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

Low Concentrations of Pyridostigmine Prevent Soman-Induced Inhibition of GABAergic Transmission in the Central Nervous System: Involvement of Muscarinic Receptors

Máriton D. Santos, Edna F. R. Pereira, Yasco Aracava, Newton G. Castro, William P. Fawcett, William R. Randall and Edson X. Albuquerque
Journal of Pharmacology and Experimental Therapeutics January 2003, 304 (1) 254-265; DOI: https://doi.org/10.1124/jpet.102.043109
Máriton D. Santos
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edna F. R. Pereira
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yasco Aracava
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Newton G. Castro
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William P. Fawcett
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William R. Randall
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edson X. Albuquerque
  • 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

This study was designed to investigate the effects of the cholinesterase inhibitors soman and pyridostigmine bromide (PB) on synaptic transmission in the CA1 field of rat hippocampal slices. Soman (1–100 nM, 10–15 min) decreased the amplitude of GABAergic postsynaptic currents (IPSCs) evoked by stimulation of Schaffer collaterals and recorded from CA1 pyramidal neurons. It also decreased the amplitude and frequency of spontaneous IPSCs recorded from pyramidal neurons. Whereas the maximal effect of soman on evoked GABAergic transmission was observed at 10 nM, full cholinesterase inhibition was induced by 1 nM soman. After 10–15-min exposure of hippocampal slices to 100 nM PB, GABAergic transmission was facilitated and cholinesterase activity was not significantly affected. At nanomolar concentrations, soman and PB have no direct effect on GABAA receptors. The effects of soman and PB on GABAergic transmission were inhibited by the m2 receptor antagonist 11-[[[2-diethylamino-O-methyl]-1-piperidinyl] acetyl]-5,11-dihydrol-6H-pyridol[2,3-b][1,4]benzodiazepine-6- one (1 nM) and the m3 receptor antagonist 4-diphenylacetoxy-N-methyl-piperidine (100 nM), respectively, and by the nonselective muscarinic receptor antagonist atropine (1 μM). Thus, changes in GABAergic transmission are likely to result from direct interactions of soman and PB with m2 and m3 receptors, respectively, located on GABAergic fibers/neurons synapsing onto the neurons under study. Although the effects of 1 nM soman and 100 nM PB were diametrically opposed, they only canceled one another when PB was applied to the neurons before soman. Therefore, PB, acting via m3 receptors, can effectively counteract effects arising from the interactions of soman with m2 receptors in the brain.

Footnotes

  • This work was supported by the U.S. Army Medical and Research Development Command contract DAMD-17-95-C-5063, a grant from the Janssen Research Foundation, U.S. Public Health Service Grant NS41671, and Conselho Nacional de Pesquisa e Desenvolvimento, Brazil. A preliminary account of this study was presented at the 1999 Annual Meetings of the Society for Neurosciences (Abstr Soc Neurosci25:1972, 1999; program no. 836.5, 2002 CD-ROM).

  • DOI: 10.1124/jpet.102.043109

  • Abbreviations:
    ACh
    acetylcholine
    CNS
    central nervous system
    PB
    pyridostigmine bromide
    AFDX-116
    11-[[[2-diethylamino-O-methyl]-1-piperidinyl]acetyl]-5,11-dihydrol-6H-pyridol[2,3-b][1,4]benzodiazepine-6-one
    ACSF
    artificial cerebrospinal fluid
    PSC
    postsynaptic current
    ANOVA
    analysis of variance
    CNQX
    6-cyano-7-nitroquinoxaline-2,3-dione
    APV
    2-amino-5-phosphonovaleric acid
    4-DAMP
    4-diphenylacetoxy-N-methylpiperidine
    MLA
    methyllycaconitine
    DHβE
    dihydro-β-erythroidine
    EPSC
    excitatory postsynaptic current
    IPSC
    inhibitory postsynaptic current
    nAChR
    nicotinic acetylcholine receptor
    VX
    O-ethylS-[2(diisopropylamino)ethyl]methylphosphonothioate
    QX-314
    N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide
    • Received August 16, 2002.
    • Accepted September 11, 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: 304 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 304, Issue 1
1 Jan 2003
  • 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.
Low Concentrations of Pyridostigmine Prevent Soman-Induced Inhibition of GABAergic Transmission in the Central Nervous System: Involvement of Muscarinic Receptors
(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

Low Concentrations of Pyridostigmine Prevent Soman-Induced Inhibition of GABAergic Transmission in the Central Nervous System: Involvement of Muscarinic Receptors

Máriton D. Santos, Edna F. R. Pereira, Yasco Aracava, Newton G. Castro, William P. Fawcett, William R. Randall and Edson X. Albuquerque
Journal of Pharmacology and Experimental Therapeutics January 1, 2003, 304 (1) 254-265; DOI: https://doi.org/10.1124/jpet.102.043109

Citation Manager Formats

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

Share
Research ArticleNEUROPHARMACOLOGY

Low Concentrations of Pyridostigmine Prevent Soman-Induced Inhibition of GABAergic Transmission in the Central Nervous System: Involvement of Muscarinic Receptors

Máriton D. Santos, Edna F. R. Pereira, Yasco Aracava, Newton G. Castro, William P. Fawcett, William R. Randall and Edson X. Albuquerque
Journal of Pharmacology and Experimental Therapeutics January 1, 2003, 304 (1) 254-265; DOI: https://doi.org/10.1124/jpet.102.043109
Reddit logo Twitter logo Facebook 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

  • Substituted Tryptamine Activity at 5-HT Receptors and SERT
  • KRM-II-81 Analogs
  • VTA muscarinic M5 receptors and effort-choice behavior
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics