Glutamate-containing dipeptides do not modulate ligand binding at excitatory amino acid receptors.
Dipeptides of the structure X-Glu (e.g. X = Phe, Leu) have been proposed as allosteric modulators of excitatory amino acid receptors in rat brain membranes. Here we report that these dipeptides reduce the binding of L-[3H]Glu (predominantly N-methyl-D-aspartate-sensitive sites) and of [3H]kainate to postsynaptic density preparations isolated from rat brain. However, several observations indicate that the effects of these dipeptides are mediated not by allosteric modulation, but by free L-Glu liberated by the actions of a membrane-associated aminopeptidase. The absolute and relative potencies of the dipeptides are similar at all acidic amino acid binding sites examined to date, suggesting the involvement of a factor with similar activity at each site (e.g. L-Glu). N-Acetyl-Met-Glu is a weak inhibitor of L-Glu and kainate binding, and N-blocked peptides are known to be poor substrates of aminopeptidases. Bestatin, an inhibitor of aminopeptidases, decreases or abolishes the effects of substrate dipeptides on L-Glu and kainate receptor binding, while having no effect itself.
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000494:Allosteric Regulation; D000596:Amino Acids / Q000378:metabolism; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000818:Animals; D001667:Binding, Competitive; D004151:Dipeptides / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051381:Rats; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D015763:2-Amino-5-phosphonovalerate; D000596:Amino Acids; D000626:Aminopeptidases; D004151:Dipeptides; D005971:Glutamates; D007608:Kainic Acid; D007930:Leucine; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C012211:ubenimex; C031231:2-amino-7-phosphonoheptanoic acid