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Title 

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

Authors 

So Young SeoBong Sik YunIn Ja RyooJun Sub ChoiChoun Ki JooSu Youne ChangJun Mo ChungSei Kwan OhByoung Joo GwagIck Dong Yoo

Publisher 

American Society for Pharmacology and Experimental Therapeutics (ASPET)

Issue Date 

2001

Citation 

Journal of Pharmacology and Experimental Therapeutics, vol. 299, no. 1, pp. 377-384

Keywords 

alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acidcomplestatinkainic acidkainic acid receptor antagonistn methyl dextro aspartic acidn methyl dextro aspartic acid receptor blocking agentanimal cellbrain celloxidative stresspriority journal

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.

ISSN 

0022-3565

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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