Displacement of excitatory amino acid receptor ligands by acidic oligopeptides

A number of L-glutamyl and L-aspartyl dipeptides, glutathione, gamma-D-glutamylglycine and gamma-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, the L enanthiomorphs of gamma-glutamyl peptides were more potent displacers than gamma-D-glutamylglycine and -taurine but the latter were more specific for the quisqualate type of receptors. gamma-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 gamma-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. gamma-L-Glutamylaminomethylsulphonate was most effective in the binding of APH. The most potent gamma-L-glutamyl peptides (glutathione, gamma-L-glutamyl-L-glutamate, -L-aspartate, and -glycine) may act as endogenous modulators of excitatory aminoacidergic neurotransmission.