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, Ick Dong Yoo

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)377-384
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume299
Issue number1
StatePublished - Oct 9 2001

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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