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Complestatin is a noncompetitive peptide antagonist of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors: secure blockade of ischemic neuronal death.

Authors
Seo, SY; Yun, BS; Ryoo, IJ; Choi, JS; Joo, CK; Chang, SY; Chung, JM; Oh, S; Gwag, BJ; Yoo, ID
Citation
The Journal of pharmacology and experimental therapeutics, 299(1):377-384, 2001
Journal Title
The Journal of pharmacology and experimental therapeutics
ISSN
0022-35651521-0103
Abstract
Complestatin, a peptide derived from Streptomyces, was found to protect cultured cortical neurons from excitotoxicity induced by N-methyl-D-aspartate (NMDA), alpha-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.
MeSH terms
AnimalsApoptosis/drug effectsBrain Ischemia/pathology*Calcium/metabolismCell Death/drug effectsChlorophenols/pharmacology*Excitatory Amino Acid Agonists/toxicityExcitatory Amino Acid Antagonists/pharmacology*Glucose/deficiencyKainic Acid/antagonists & inhibitorsKainic Acid/toxicityMiceNeurons/drug effects*Neuroprotective Agents/pharmacology*Oligopeptides/pharmacology*Oxidative Stress/drug effectsOxygen/physiologyPatch-Clamp TechniquesPeptides, Cyclic*Receptors, AMPA/antagonists & inhibitors*Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors*Retinal Vessels/drug effectsRetinal Vessels/physiology
PMID
11561102
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
곽, 병주
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