Low-concentration N-acetylaspartylglutamate suppresses the climbing fiber response of Purkinje cells in guinea pig cerebellar slices and the responses to excitatory amino acids of Xenopus laevis oocytes injected with cerebellar mRNA.

Whether N-acetylaspartylglutamate (NAAG) at micromolar concentrations shows a modulatory action on the synaptic transmission mediated by excitatory amino acids was investigated using Guinea pig cerebellar slices and the Xenopus laevis oocytes injected with mRNA from Guinea pig cerebellum. The climbing fiber response consisted of an excitatory postsynaptic potential (EPSP) and a plateau potential intracellularly recorded from Purkinje cell dendrite was depressed by 30 microM NAAG; the EPSP was decreased by about 21% in amplitude and the plateau potential was depressed by about 42% in duration. The depolarization induced by L-aspartate, L-glutamate, N-methyl-D-aspartate and quisqualate in mRNA-injected Xenopus oocytes were non-selectively antagonized by 0.5 microM-5 microM NAAG, the mean % blockade by 5 microM NAAG being about 38%. Higher concentrations (greater than 100 microM) of NAAG alone by 33% on average by 10 microM NAAG. These results suggest the possibility that micromolar concentrations of NAAG may attenuate the synaptic transmission mediated by glutamate receptors not only by blocking postsynaptic receptors but also by facilitating the high-affinity re-uptake of transmitter amino acids.