Synaptosomal transport of radiolabel from N-acetyl-aspartyl-[3H]glutamate suggests a mechanism of inactivation of an excitatory neuropeptide.

Blakely RD, Ory-Lavollée L, Thompson RC, Coyle JT
J Neurochem. 1986 47 (4): 1013-9

PMID: 2875126 · DOI:10.1111/j.1471-4159.1986.tb00714.x

This study was undertaken to explore in synaptosomal preparations the disposition of N-acetyl-aspartyl-glutamate (NAAG), an endogenous acidic dipeptide neurotransmitter candidate. Radiolabel from N-acetyl-aspartyl[3H]glutamate was taken up rapidly into an osmotically sensitive compartment by rat brain synaptosomal preparations in a sodium-, temperature-, and time-dependent manner. HPLC analysis of the accumulated radiolabel indicated that the bulk of the tritium cochromatographed with glutamic acid and not with NAAG. In contrast, [14C]NAAG, labeled on the N-terminal acetate, was not taken up by the synaptosomal preparation. All effective inhibitors of synaptosomal, Na+-dependent [3H]glutamate uptake were found to exhibit similar potency in inhibiting uptake of tritium derived from [3H]NAAG. However, certain alpha-linked acidic dipeptides, structurally similar to NAAG, as well as the potent convulsant quisqualic acid inhibited synaptosomal transport of [3H]NAAG but were ineffective as inhibitors of [3H]glutamate transport. Together with a demonstration of disparities between the regional accumulation of radiolabel from [3H]NAAG and high-affinity [3H]glutamate uptake, these data suggest the presence in brain of a specific peptidase targeting carboxy-terminal glutamate-containing dipeptides that may be coupled to the Na+-dependent glutamate transporter. These findings provide a possible mechanism for NAAG inactivation subsequent to its release from nerve endings.

MeSH Terms (16)

Amino Acids Animals Biological Transport Brain Dipeptides Glutamates Glutamic Acid Kinetics Male Oxadiazoles Quisqualic Acid Rats Rats, Inbred Strains Sodium Synaptosomes Tritium

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