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

Direct inhibition of 5-hydroxytryptamine3 receptors by antagonists of L-type Ca2+ channels.

A C Hargreaves, M J Gunthorpe, C W Taylor and S C Lummis
Molecular Pharmacology November 1996, 50 (5) 1284-1294;
A C Hargreaves
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M J Gunthorpe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C W Taylor
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S C Lummis
  • 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

Homopentameric complexes of either the A or As subunit of the 5-hydroxytryptamine3 receptor form Ca(2+)-permeable channels that can be activated by the selective agonist 1-(m-chlorophenyl)-biguanide (mCPBG). In both N1E-115 neuroblastoma cells and human embryonic kidney 293 cells stably expressing the 5-HT3 receptor As subunit, (+)-verapamil, (-)-verapamil, diltiazem, and nimodipine caused reversible and concentration-dependent (IC50 = 2.5-6.5 microM) inhibition of the increases in cytosolic [Ca2+] evoked by mCPBG. In voltage-clamped human embryonic kidney 293 cells stably expressing the 5-HT3 receptor As subunit, similar concentrations of the Ca2+ channel antagonists (IC50 = 3.0-6.8 microM) accelerated the rate at which 5-HT-evoked currents decayed without affecting the amplitude of the peak current. In equilibrium competition binding assays to membranes from Sf9 cells infected with the 5-HT3 receptor As subunit, [3H]mCPBG and [3H]granisetron were displaced by (+)-verapamil, (-)-verapamil, and diltiazem; (+)-verapamil was approximately 10-fold more potent than (-)-verapamil and approximately-30-fold more potent than diltiazem. Nimodipine neither displaced [3H]granisetron binding nor affected its displacement by diltiazem and (+)-verapamil. The stereoselectivity of verapamil binding, which contrasts with the similar potency of each isomer in functional assays, was maintained when the incubations were performed at 20 degrees or when an antagonist of the 5-HT3 receptor, [3H]granisetron, was used as the radioligand. The interaction between verapamil and either [3H]mCPBG or [3H]granisetron binding was not competitive. We conclude that the inhibition of [3H]mCPBG binding by diltiazem and verapamil is mediated by a site that is distinct from both the agonist-binding site and from the site through which nimodipine inhibits 5-HT3 receptor function. Our results provide evidence for allosteric regulation of agonist binding to 5-HT3 receptors and the first example of a ligandgated ion channel whose function is directly inhibited by members of all three major classes of L-type Ca2+ channel antagonists.

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. 50, Issue 5
1 Nov 1996
  • 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.
Direct inhibition of 5-hydroxytryptamine3 receptors by antagonists of L-type Ca2+ channels.
(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

Direct inhibition of 5-hydroxytryptamine3 receptors by antagonists of L-type Ca2+ channels.

A C Hargreaves, M J Gunthorpe, C W Taylor and S C Lummis
Molecular Pharmacology November 1, 1996, 50 (5) 1284-1294;

Citation Manager Formats

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

Share
Abstract

Direct inhibition of 5-hydroxytryptamine3 receptors by antagonists of L-type Ca2+ channels.

A C Hargreaves, M J Gunthorpe, C W Taylor and S C Lummis
Molecular Pharmacology November 1, 1996, 50 (5) 1284-1294;
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