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

L O Porciúncula; A Dal-Pizzol Jr; A S Coitinho; T Emanuelli; D O Souza; M Wajner

doi:10.1016/s0022-510x(99)00307-x

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

J Neurol Sci. 2000 Feb 15;173(2):93-6. doi: 10.1016/s0022-510x(99)00307-x.

Authors

L O Porciúncula¹, A Dal-Pizzol Jr, A S Coitinho, T Emanuelli, D O Souza, M Wajner

Affiliation

¹ Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, Brazil.

PMID: 10675650
DOI: 10.1016/s0022-510x(99)00307-x

Abstract

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, respectively. [3H]Glutamate uptake into synaptosomes was inhibited by approximately 50% by 1 mM glutaric acid, corresponding to the concentration found in brain of glutaric acidemic children. In addition, in the presence of extracellular Na+ concentrations, the same dose of glutaric acid decreased by about 30% [3H]glutamate binding to brain plasma membranes. The results indicate that the inhibition of both glutamate uptake into synaptosomes and glutamate binding to plasma synaptic membranes by the metabolite could result in elevated concentrations of the excitatory neurotransmitter in the synaptic cleft, potentially causing excitotoxicity to neural cells, a fact that may be related to the brain damage characteristic of glutaric acidemia type I.

MeSH terms

ATP-Binding Cassette Transporters / antagonists & inhibitors
Amino Acid Metabolism, Inborn Errors / metabolism
Amino Acid Transport System X-AG
Animals
Cell Membrane / metabolism*
Convulsants / pharmacology*
Depression, Chemical
Glutamate Decarboxylase / antagonists & inhibitors
Glutamic Acid / metabolism*
Glutarates / pharmacology*
Glutaryl-CoA Dehydrogenase
Male
Nerve Tissue Proteins / antagonists & inhibitors
Neurotoxins / pharmacology*
Oxidoreductases / deficiency
Oxidoreductases Acting on CH-CH Group Donors*
Rats
Rats, Wistar
Sodium / pharmacology
Synaptosomes / drug effects*
Synaptosomes / metabolism
gamma-Aminobutyric Acid / biosynthesis
gamma-Aminobutyric Acid / deficiency

Substances

ATP-Binding Cassette Transporters
Amino Acid Transport System X-AG
Convulsants
Glutarates
Nerve Tissue Proteins
Neurotoxins
Glutamic Acid
gamma-Aminobutyric Acid
Sodium
Oxidoreductases
Oxidoreductases Acting on CH-CH Group Donors
Glutaryl-CoA Dehydrogenase
Glutamate Decarboxylase
glutaric acid