Inhibition of glutamate uptake into synaptic vesicles of rat brain by the metabolites accumulating in maple syrup urine disease.
J Neurol Sci
; 181(1-2): 44-9, 2000 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-11099711
Maple syrup urine disease is an inherited metabolic disorder characterized by tissue accumulation of branched-chain amino acids and their corresponding keto acids in the affected children. Although this disorder is predominantly characterized by neurological symptoms, only few studies were carried out to investigate its neuropathology. In this study we investigated the effect of the metabolites accumulating in maple syrup urine disease on the in vitro uptake of [3H]glutamate by synaptic vesicles of rat brain. Synaptic vesicle preparations from whole brain of male adult Wistar rats (200-250 g) were incubated with the branched-chain amino acids and their corresponding keto acids at final concentrations ranging from 0.25 to 10 mM for the determination of glutamate uptake. Glutamate uptake was significantly inhibited by L-leucine, L-isoleucine, L-2-ketoisocaproic acid and L-2-keto-3-methylvaleric acid by approximately 60%, whereas L-valine and L-2-ketoisovaleric acid showed no effect. We also verified that the metabolites probably act by competitive inhibition. Therefore, it is possible that extracellular glutamate levels may be increased in maple syrup urine disease and that excitotoxicity may be involved in the neuropathology of this disorder.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vesículas Sinápticas
/
Encéfalo
/
Ácido Glutâmico
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Doença da Urina de Xarope de Bordo
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
J Neurol Sci
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Holanda