Quantitative differences in the effects of de novo produced and exogenous kynurenic acid in rat brain slices

Neurosci Lett. 1999 Oct 22;274(2):111-4. doi: 10.1016/s0304-3940(99)00690-4.

Abstract

Kynurenic acid (KYNA) is an antagonist of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors and it blocks the glycine site of the NMDA receptor preferentially (IC50 = 7.9 microM). KYNA is produced endogenously by transamination of its precursor L-kynurenine (L-KYN). We tested the hypothesis that effects of endogenous, de novo produced KYNA, following bath-application of L-KYN to slices, would be different than effects of commercially-synthesized (exogenous) KYNA. The ability to block spontaneous epileptiform activity, induced by lowering extracellular magnesium, was examined in area CA3 of hippocampus and the entorhinal cortex. At a concentration of 200 microM L-KYN, which produced 0.89 +/- 0.20 microM KYNA, there were fewer slices with spontaneous epileptiform activity than slices exposed to 2 microM exogenous KYNA. The results indicate a more potent neuromodulatory action of endogenous KYNA than has been previously realized.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Buffers
  • Entorhinal Cortex / drug effects
  • Entorhinal Cortex / metabolism
  • Entorhinal Cortex / physiopathology
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy
  • Evoked Potentials / drug effects
  • Excitatory Amino Acid Antagonists / metabolism*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Glycine / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Kynurenic Acid / metabolism*
  • Kynurenic Acid / pharmacology*
  • Magnesium / pharmacology
  • Male
  • Neurotransmitter Agents / metabolism
  • Neurotransmitter Agents / pharmacology
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Tryptophan / metabolism

Substances

  • Buffers
  • Excitatory Amino Acid Antagonists
  • Neurotransmitter Agents
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Tryptophan
  • Kynurenic Acid
  • Magnesium
  • Glycine