Characterization of the interactions of N-acetyl-aspartyl-glutamate with [3H]L-glutamate receptors.
The specific binding of [3H]L-glutamate and its displacement by N-acetyl-aspartyl glutamate, a peptide endogenous to brain, has been examined in nine regions of the central nervous system. N-acetyl-aspartyl-glutamate caused only a partial displacement of [3H]L-glutamate specific binding with an uneven regional distribution of maximal inhibition, ranging from 61% in the thalamus to 40% in the cerebral cortex and the hippocampus. The maximal displacement of specifically bound [3H]L-glutamate by N-acetyl-aspartyl-glutamate was not significantly affected by calcium added to chloride containing buffer; however, in the absence of chloride or calcium, no significant displacement of [3H]L-glutamate by N-acetyl-aspartyl-glutamate was observed. N-Acetyl-aspartyl-glutamate displayed the highest affinity for the chloride-dependent sites labeled by [3H]L-glutamate among all peptide analogues examined. These results suggest that N-acetyl-aspartyl-glutamate may play a role as an endogenous excitatory peptide in the mammalian central nervous system and raise the question whether endogenous brain peptides enriched in acidic amino acids may serve as excitatory transmitters.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D004151:Dipeptides / Q000502:physiology*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017470:Receptors, Glutamate
D002712:Chlorides; D004151:Dipeptides; D005971:Glutamates; D011956:Receptors, Cell Surface; D017470:Receptors, Glutamate; C027172:isospaglumic acid; D018698:Glutamic Acid; D002118:Calcium