Release of endogenous N-acetylaspartylglutamate (NAAG) and uptake of [3H]NAAG in guinea pig cerebellar slices.

For the purpose of obtaining chemical information about the physiological role of N-acetylaspartylglutamate (NAAG), the release of endogenous NAAG from and the uptake of [3H]NAAG by Guinea pig cerebellar slices were investigated in comparison with L-aspartate (Asp) and L-glutamate (Glu). Although endogenous NAAG was found to be released spontaneously from the slices as is endogenous Asp and Glu, high-K+-induced facilitation of release occurred only for endogenous Asp and Glu in a Ca2+-dependent manner, but not for NAAG. It was confirmed that [3H]NAAG itself was taken up in a Na+-dependent manner by the slices by two low-affinity processes with small Vmax values, and labeled Glu and glutamine were detected as the metabolites of [3H]NAAG in the slices. The [3H]NAAG uptake was slower than that of labeled Glu and was significantly depressed by NAAG, Asp, Glu and D-aspartate, but not affected by gamma-aminobutyrate, suggesting that NAAG may share a common uptake carrier with excitatory amino acids. These results suggest that endogenous NAAG may act extracellularly, but the amount of endogenous NAAG released from nerve terminals by presynaptic depolarization may be very small if any, and also that spontaneously liberated NAAG can be inactivated by low-affinity uptake systems, at least, in the Guinea pig cerebellum.