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
Research ArticleArticle

[3H]R214127: A Novel High-Affinity Radioligand for the mGlu1 Receptor Reveals a Common Binding Site Shared by Multiple Allosteric Antagonists

Hilde Lavreysen, Cor Janssen, François Bischoff, Xavier Langlois, Josée E. Leysen and Anne S. J. Lesage
Molecular Pharmacology May 2003, 63 (5) 1082-1093; DOI: https://doi.org/10.1124/mol.63.5.1082
Hilde Lavreysen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cor Janssen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
François Bischoff
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xavier Langlois
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Josée E. Leysen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne S. J. Lesage
  • 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

R214127 was shown to be a potent and noncompetitive metabotropic glutamate 1 (mGlu1) receptor-selective antagonist. The kinetics and pharmacology of [3H]1-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenyl-1-ethanone (R214127) binding to rat mGlu1a receptor Chinese hamster ovary (CHO)-dhfr− membranes was investigated, as well as the distribution of [3H]R214127 binding in rat brain tissue and sections. Specific binding to rat mGlu1a receptor CHO-dhfr− membranes was ∼92% of total and was optimal at 4°C. Full association was reached within 5 min, and [3H]R214127 bound to a single binding site with an apparent KD of 0.90 ± 0.14 nM and aBmax of 6512 ± 1501 fmol/mg of protein. Inhibition experiments showed that [3H]R214127 binding was completely blocked by 2-quinoxaline-carboxamide-N-adamantan-1-yl (NPS 2390), (3aS,6aS)-6a-naphtalan-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c]furan-1-on (BAY 36-7620), and 7-(hydroxyimino)cyclo-propa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt), but was not displaced by competitive mGlu1 receptor ligands such as glutamate and quisqualate, suggesting that R214127, NPS 2390, BAY 36-7620, and CPCCOEt bind to the same site or mutually exclusive sites. Experiments using rat cortex, striatum, hippocampus and cerebellum revealed that [3H]R214127 labeled a single high-affinity binding site (KD ∼ 1 nM).Bmax values were highest in the cerebellum (4302 ± 2042 fmol/mg of protein) and were 741 ± 48, 688 ± 125, and 471 ± 68 fmol/mg of protein in the striatum, hippocampus, and cortex, respectively. The distribution of [3H]R214127 binding in rat brain was investigated in more detail by radioligand autoradiography. A high density of binding sites was detected in the molecular layer of the cerebellum. Moderate labeling was seen in the CA3 and dentate gyrus of the hippocampus, thalamus, olfactory tubercle, amygdala, and substantia nigra reticulata. The cerebral cortex, caudate putamen, ventral pallidum, and nucleus accumbens showed lower labeling. The high affinity and selectivity of [3H]R214127 for mGlu1 receptors renders this compound the ligand of choice to study the native mGlu1 receptor in brain.

Footnotes

  • Abbreviations:
    mGlu
    metabotropic glutamate
    CHO-dhfr− cells
    dihydrofolate reductase-deficient Chinese hamster ovary cells
    R214127
    1-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenyl-1-ethanone
    R193845
    2-amino-3-ethyl-6-quinolinyl)(4-methoxycyclohexyl)methanone
    GTPγS
    guanosine-5′-O-(3-thio)triphosphate
    MK-801
    (5R,10S)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine
    CGP39653
    dl-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid
    LY341495
    (2S,1′S,2′S)-2-(9-xanthylmethyl)-2-(2′-carboxycyclopropyl)-glycine
    MPEP
    2-methyl-6-(phenylethynyl)pyridine
    (S)-4C3HPG
    (S)-4-carboxy-3-hydroxyphenylglycine
    (1S,3R)-ACPD
    (1S,3R)-1-aminocyclopentane-trans-1,3-dicarboxylic acid
    (S)-3,5-DHPG
    (S)-3,5-dihydroxyphenylglycine
    (S)-4CPG
    (S)-4-carboxyphenylglycine
    AIDA
    (R,S)-1-aminoindan-1,5 dicarboxylic acid
    MCPG
    (S)-α-methyl-4-carboxyphenylglycine
    CPCCOEt
    7-(hydroxyimino)cyclo-propa[b]chromen-1a-carboxylate ethyl ester
    BAY 36-7620
    (3aS,6aS)-6a-naphtalan-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c]furan-1-on
    NPS 2390
    2-quinoxaline-carboxamide-N-adamantan-1-yl
    IP
    inositol phosphate
    Ro 48-8587
    9-imidazol-1-yl-8-nitro-2,3,5,6-tetrahydro[1,2,4]triazolo[1,5-c]quinazoline-2,5-dione
    L689560
    trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonyl amino-1,2,3,4-tetrahydroquinoline
    LY367385
    (+)-2-methyl-4-carboxyphenylglycine
    Ka
    acid dissociation constant
    P
    partition coefficient
    D
    partition coefficient at particular pH
    • Received October 21, 2002.
    • Accepted February 4, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

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: 63 (5)
Molecular Pharmacology
Vol. 63, Issue 5
1 May 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 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.
[3H]R214127: A Novel High-Affinity Radioligand for the mGlu1 Receptor Reveals a Common Binding Site Shared by Multiple Allosteric Antagonists
(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
Research ArticleArticle

[3H]R214127: A Novel High-Affinity Radioligand for the mGlu1 Receptor Reveals a Common Binding Site Shared by Multiple Allosteric Antagonists

Hilde Lavreysen, Cor Janssen, François Bischoff, Xavier Langlois, Josée E. Leysen and Anne S. J. Lesage
Molecular Pharmacology May 1, 2003, 63 (5) 1082-1093; DOI: https://doi.org/10.1124/mol.63.5.1082

Citation Manager Formats

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

Share
Research ArticleArticle

[3H]R214127: A Novel High-Affinity Radioligand for the mGlu1 Receptor Reveals a Common Binding Site Shared by Multiple Allosteric Antagonists

Hilde Lavreysen, Cor Janssen, François Bischoff, Xavier Langlois, Josée E. Leysen and Anne S. J. Lesage
Molecular Pharmacology May 1, 2003, 63 (5) 1082-1093; DOI: https://doi.org/10.1124/mol.63.5.1082
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
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • EIPA, HMA and SMN2 gene regulation
  • Clc-2 has minor role in intestinal Cl- secretion
  • Resveratrol acts as an NR4A1 antagonist in lung cancer.
Show more Article

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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics