Quinolinic acid inhibits glutamate uptake into synaptic vesicles from rat brain.
Quinolinic acid (QA) is an endogenous and potent neurotoxin associated with the neurotoxicity of various common diseases. The uptake of neurotransmitters into synaptic vesicles is an important event involved in the storage and release of neurotransmitters by vesicles. The influence of QA on the uptake of glutamate, GABA and glycine into rat brain synaptic vesicles was investigated. QA (0.3-10 mM) significantly inhibited (>50%) the uptake of glutamate into synaptic vesicles, whereas QA at concentrations up to 10 mM had no significant effect on GABA or glycine uptake. Such results indicate that QA is able to selectively inhibit the vesicular uptake of glutamate, without interfering with the uptake of the inhibitory neurotransmitters GABA and glycine. These findings might be related to the neurotoxic effects of QA in the brain.
Tavares
R G
RG
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
Tasca
C I
CI
Santos
C E
CE
Wajner
M
M
Souza
D O
DO
Dutra-Filho
C S
CS
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D005998:Glycine / Q000493:pharmacokinetics; D008297:Male; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D017378:Quinolinic Acid; D005998:Glycine