Quinolinic acid inhibits glutamate uptake into synaptic vesicles from rat brain

Neuroreport. 2000 Feb 7;11(2):249-53. doi: 10.1097/00001756-200002070-00005.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Brain / metabolism*
  • Dose-Response Relationship, Drug
  • Glutamic Acid / pharmacokinetics*
  • Glycine / pharmacokinetics
  • Male
  • Quinolinic Acid / toxicity*
  • Rats
  • Rats, Wistar
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / metabolism*
  • gamma-Aminobutyric Acid / pharmacokinetics

Substances

  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Quinolinic Acid
  • Glycine