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

Complestatin Is a Noncompetitive Peptide Antagonist of N-Methyl-d-aspartate and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/Kainate Receptors: Secure Blockade of Ischemic Neuronal Death

So Young Seo, Bong-Sik Yun, In-Ja Ryoo, Jun-Sub Choi, Choun-Ki Joo, Su-Youne Chang, Jun-Mo Chung, Seikwan Oh, Byoung Joo Gwag and Ick Dong Yoo
Journal of Pharmacology and Experimental Therapeutics October 2001, 299 (1) 377-384;
So Young Seo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bong-Sik Yun
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
In-Ja Ryoo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jun-Sub Choi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Choun-Ki Joo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Su-Youne Chang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jun-Mo Chung
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Seikwan Oh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Byoung Joo Gwag
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ick Dong Yoo
  • 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

Complestatin, a peptide derived from Streptomyces, was found to protect cultured cortical neurons from excitotoxicity induced by N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or kainate. This neuroprotective behavior of complestatin was attributed to a blockade of Ca2+ ion entry and accumulation, after the activation of NMDA and AMPA/kainate receptors. Complestatin reversibly interfered with NMDA- and AMPA-mediated excitatory synaptic transmission. Complestatin also protected cortical neurons from prolonged deprivation of oxygen and glucose, more effectively than combined antagonists of NMDA and AMPA/kainate receptors. Neurotoxicity, evolving within 1 to 2 days after continuous exposure to combined NMDA and AMPA/kainate antagonists, was not observed in cortical cell cultures that were exposed to complestatin. Finally, complestatin dose dependently prevented neuronal death evolving within the inner nuclear and ganglion cell layers, after transient retinal ischemia. We conclude that complestatin possesses novel pharmacological properties that effectively prevent excitotoxicity under certain pathological conditions.

Footnotes

  • This work was supported in part by G7 grants (to I.D.Y.) from the Korean Ministry of Science and Technology, National Research Laboratory grants (to B.J.G.), and by the Korea Science and Engineering Foundation grant through Center for Cell Signaling Research Fund (to J.-M.C.).

  • Abbreviations:
    NMDA
    N-methyl-d-aspartate
    AMPA
    α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
    DIV
    days in vitro
    LDH
    lactate dehydrogenase
    [Ca2+]I
    intracellular calcium concentration
    fura-2
    1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2′-amino-5′-methylphenoxy)-ethane-N,N,N′,N′-tetraacetic acid
    CNQX
    6-cyano-2,3-dihydroxy-7-nitroquinoxaline
    • Received April 16, 2001.
    • Accepted July 9, 2001.
  • 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: 299 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 1
1 Oct 2001
  • 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.
Complestatin Is a Noncompetitive Peptide Antagonist of N-Methyl-d-aspartate and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/Kainate Receptors: Secure Blockade of Ischemic Neuronal Death
(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

Complestatin Is a Noncompetitive Peptide Antagonist of N-Methyl-d-aspartate and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/Kainate Receptors: Secure Blockade of Ischemic Neuronal Death

So Young Seo, Bong-Sik Yun, In-Ja Ryoo, Jun-Sub Choi, Choun-Ki Joo, Su-Youne Chang, Jun-Mo Chung, Seikwan Oh, Byoung Joo Gwag and Ick Dong Yoo
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 377-384;

Citation Manager Formats

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

Share
Research ArticleNEUROPHARMACOLOGY

Complestatin Is a Noncompetitive Peptide Antagonist of N-Methyl-d-aspartate and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/Kainate Receptors: Secure Blockade of Ischemic Neuronal Death

So Young Seo, Bong-Sik Yun, In-Ja Ryoo, Jun-Sub Choi, Choun-Ki Joo, Su-Youne Chang, Jun-Mo Chung, Seikwan Oh, Byoung Joo Gwag and Ick Dong Yoo
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 377-384;
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

  • Glycine receptor modulation using monoclonal antibodies
  • Iclepertin (BI 425809) in Schizophrenia-Related Models
  • D1 Agonist Versus Methylphenidate on PFC Working Memory
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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics