The Janus-face kynurenic acid

J Neural Transm (Vienna). 2008 Aug;115(8):1087-91. doi: 10.1007/s00702-008-0052-5. Epub 2008 Apr 30.

Abstract

Kynurenic acid is an endogenous product of the tryptophan metabolism. Studies on the mechanism of its action have revealed that kynurenic acid at high concentrations is a competitive antagonist of the N-methyl-D-aspartate receptor and acts as a neuroprotectant in different neurological disorders. This in vitro investigation was designed to show that kynurenic acid acts differently at low concentrations. In vitro electrophysiological examinations on the young rat hippocampus confirmed the well-known finding that kynurenic acid in micromolar concentrations exerts an inhibitory effect. However, in nanomolar concentrations, kynurenic acid does not give rise to inhibition, but in fact facilitates the field excitatory postsynaptic potentials. The results available so far are compatible with the idea that kynurenic acid in the concentration range between a few hundred nanomolar and micromolar displays different effects. Its probable action on different receptors, inducing the different mechanisms, is discussed. The findings strongly suggest the neuromodulatory role of kynurenic acid under both physiological and pathological circumstances.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Hippocampus / drug effects*
  • In Vitro Techniques
  • Kynurenic Acid / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Tryptophan / pharmacology

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Tryptophan
  • Kynurenic Acid