Effect of aspartame on N-methyl- d-aspartate-sensitive l-[ 3H]glutamate binding sites in rat brain synaptic membranes

Abstract

Aspartame ( l-aspartyl- l-phenylalanine methyl ester), an artificial low-calorie sweetener, was shown to dose-dependently inhibit l-[ 3H]glutamate binding to its N-methyl- d-aspartate-specific receptors. l-Aspartic acid, a major endogenous metabolite of aspartame, inhibited the binding more stronger than aspartame, while the other metabolites, l-phenylalanine and methanol, had no effect at the same concentration. Aspartame caused a significant change in the affinities of l-[ 3H]glutamate binding without altering the V max values of the binding, suggesting the inhibition is competitive. These in vitro findings suggested that aspartame may act directly on the N-methyl- d-aspartate-sensitive glutamate recognition sites in the brain synaptic membranes.