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

Abstract

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 μM NAAG; the EPSP was decreased by about 21% in amplitude and the plateau potential was depressed by about 42% in duration. The depolarizations induced by l-aspartate, l-glutamate, N-methyl->d-aspartate and quisqualate in mRNA-injected Xenopus oocytes were non-selectively antagonized by 0.5 μM – 5μM NAAG, the mean % blockade by 5 μM NAAG being about 38%. Higher concentrations (100 μM) of NAAG alone depolarized mRNA-injected oocytes. On the other hand, the high-affinity uptake of l-[ 3H]aspartate by cerebellar slices was enhanced by 33% on average by 10 μM 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.