Inhibition of synaptosomal [H-3]glutamate uptake and [H-3]glutamate binding to plasma membranes from brain of young rats by glutaric acid in vitro

Synaptosomes and plasma membrane preparations from brain of 30-day-old rats were incubated with glutaric acid at final concentrations ranging from 10 nM to 1 mM for the determination of glutamate uptake and binding, respectiv ely. [H-3]Glutamate uptake into synaptosomes was inhibited by approximately 50% by 1 mM glutaric acid, corresponding to the concentration found in bra in of glutaric acidemic children. In addition, in the presence of extracell ular Na+ concentrations, the same dose of glutaric acid decreased by about 30% [H-3]glutamate binding to brain plasma membranes. The results indicate that the inhibition of both glutamate uptake into synaptosomes and glutamat e binding to plasma synaptic membranes by the metabolite could result in el evated concentrations of the excitatory neurotransmitter in the synaptic cl eft, potentially causing excitotoxicity to neural cells, a fact that may be related to the brain damage characteristic of glutaric acidemia type I. (C ) 2000 Elsevier Science B.V. All rights reserved.