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Displacement of excitatory amino acid receptor ligands by acidic oligopeptides

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Abstract

A number ofD-glutamyl andL-aspartyl dipeptides, glutathione, γ-D-glutamylglycine and γ-D-glutamyltaurine, were tested for their efficacy to displace ligands specific for different subtypes of excitatory amino acid receptors from rat brain synaptic membranes. In general, theL enanthiomorphs of γ-glutamyl peptides were more potent displacers than γ-D-glutamylglycine and-taurine but the latter were more specific for the quisqualate type of receptors. γ-L-glutamyl-L-glutamate was the most effective dipeptide in displacing the binding of glutamate, 2-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) and 2-amino-5-phosphonoheptanoate (APH), whereas γ-L-glutamyl-L-aspartate was the most effective in the binding of kainate. Both oxidized and reduced glutathione were inhibitory, being most potent in the binding of AMPA. γ-L-Glutamylaminomethylsulphonate was most effective in the binding of APH. The most potent γ-L-glutamyl peptides (glutathione, γ-L-glutamyl-L-glutamate,-L-aspartate, and-glycine) may act as endogenous modulators of excitatory aminoacidergic neurotransmission.

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Varga, V., Janáky, R., Marnela, K.M. et al. Displacement of excitatory amino acid receptor ligands by acidic oligopeptides. Neurochem Res 14, 1223–1227 (1989). https://doi.org/10.1007/BF00965513

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