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.