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
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
    • 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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Abstract

Meproadifen reaction with the ionic channel of the acetylcholine receptor: potentiation of agonist-induced desensitization at the frog neuromuscular junction.

M A Maleque, C Souccar, J B Cohen and E X Albuquerque
Molecular Pharmacology November 1982, 22 (3) 636-647;
M A Maleque
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C Souccar
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J B Cohen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E X Albuquerque
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The actions of the nicotinic noncompetitive antagonist meproadifen on both the acetylcholine (ACh) receptor-ion channel complex and electrically excitable membrane were examined in frog sciatic-nerve sartorius muscle preparations. Meproadifen (10-25 microM) blocked the nerve-evoked twitch without affecting the directly evoked twitch, the threshold, overshoot, amplitude, rate of rise, or falling phase of the directly elicited action potential in muscle. This suggests that this agent, at the concentrations that affect the nicotinic receptor, had negligible effect on the excitable membrane. In addition, the drug did not affect either the quantal content or quantal size of the end-plate potential. Meproadifen caused a voltage- and time-dependent decrease in the peak amplitude of the end-plate current (EPC) without significantly shortening the time constant of EPC decay. The voltage- and time-dependent effects of meproadifen were more pronounced at more negative potentials, as evidenced by hysteresis loops and nonlinearity in the current-voltage relationship of the EPC. Both hysteresis and nonlinearity in the current-voltage relationship of the EPC were eliminated when brief conditioning pulses were used for stepwise changes of membrane potentials. The decay time constant of the EPC in the presence of meproadifen remained an exponential function of time. Meproadifen blocked iontophoretically elicited EPCs but did not affect single-channel lifetime, conductance, or the decay time constant of the miniature EPC. Thus, the blockade was more marked on iontophoretically elicited EPCs than on miniature EPCs. Meproadifen also caused desensitization of both the junctional and extrajunctional ACh receptors, but, more important, meproadifen accelerated steady-state desensitization by several-fold (compared with the agonist). The marked depression of peak EPC amplitude and miniature EPC, its high affinity for the binding sites in the presence of the agonist, and acceleration of agonist-induced desensitization suggest that meproadifen interacts with the ACh-bound but nonconducting state of the ACh receptor-ion channel complex. Therefore, it appears that meproadifen interacts with the closed ionic channel of the ACh receptor in its resting and activated but nonconducting states, and only slightly affects the open conformation of the ionic channel.

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
Vol. 22, Issue 3
1 Nov 1982
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • 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 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.
Meproadifen reaction with the ionic channel of the acetylcholine receptor: potentiation of agonist-induced desensitization at the frog neuromuscular junction.
(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
Abstract

Meproadifen reaction with the ionic channel of the acetylcholine receptor: potentiation of agonist-induced desensitization at the frog neuromuscular junction.

M A Maleque, C Souccar, J B Cohen and E X Albuquerque
Molecular Pharmacology November 1, 1982, 22 (3) 636-647;

Citation Manager Formats

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

Share
Abstract

Meproadifen reaction with the ionic channel of the acetylcholine receptor: potentiation of agonist-induced desensitization at the frog neuromuscular junction.

M A Maleque, C Souccar, J B Cohen and E X Albuquerque
Molecular Pharmacology November 1, 1982, 22 (3) 636-647;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

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 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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics