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.
Varga
V
V
Department of Biomedical Sciences, University of Tampere, Finland.
Janáky
R
R
Marnela
K M
KM
Gulyás
J
J
Kontro
P
P
Oja
S S
SS
D000818:Animals; D001667:Binding, Competitive; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D009842:Oligopeptides; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D007051:Ibotenic Acid; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid