N-Acetyl-Aspartylglutamate Modulation of N-Methyl-D-Aspartate- Stimulated [3H]Norepinephrine Release from Rat

The release of preloaded radiolabeled norepinephnne ([3H]NE) from slices of rat hippocampus can be stimulated by excitatory amino acids that interact with the N-methyl-o-aspartate (NMDA) receptor. The acidic dipeptide N-acetyl-L-aspartylglutamate (NAAG) is colocalized with NE in the cell bodies of locus coeru-leus (the origin of the noradrenergic projections to the hippocam-pus) and the hippocampus itself. The function of NAAG in these neurons has not been demonstrated, although evidence exists that it may serve as a neuromodulator in other neuronal path-ways. NAAG inhibited the release of [3H]NE stimulated by NMDA and L-glutamate in a concentration-related manner. The maximal inhibition produced by NAAG was about 25 % of the control release stimulated by 25 M NMDA. The effects observed were caused by the intact dipeptide and not the degradation artifact