The pentylenetetrazole-induced activity in the hippocampus can be inhibited by the conversion of l-kynurenine to kynurenic acid

An in vitro study

Eva Rozsa, H. Robotka, David Nagy, T. Farkas, K. Sas, L. Vécsei, J. Toldi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The kynurenine pathway converts tryptophan into various compounds, including l-kynurenine, which in turn can be converted into the excitatory amino acid receptor antagonist kynurenic acid. The ionotropic glutamate receptors have been considered to be attractive targets for new anticonvulsants in neurological disorders such as epileptic seizure. This study was designed to examine the conversion of l-kynurenine to kynurenic acid and to investigate the effects of kynurenic acid on pentylenetetrazole-treated rat brain slices, and in parallel to draw attention to the fact that a well-designed in vitro model has many advantages in pharmacological screening. Schaffer collateral stimulation-evoked field EPSPs were recorded from area CA1 of rat hippocampal slices in vitro; drugs were bath-applied. Pretreatment with the kynurenic acid precursor l-kynurenine led to the elimination of the effect of pentylenetetrazole on hippocampal slices in vitro. N-Omega-nitro-l-arginine, which inhibits kynurenine aminotransferase I and II, abolished this neuroprotective effect. This study has furnished the first in vitro electrophysiological evidence that rat brain slices have the enzymatic capacity to convert exogenously administered l-kynurenine (16 μM) to kynurenic acid in an amount sufficient to protect them against pentylenetetrazole (1 mM)-induced hyperexcitability.

Original languageEnglish
Pages (from-to)474-479
Number of pages6
JournalBrain Research Bulletin
Volume76
Issue number5
DOIs
Publication statusPublished - Jul 30 2008

Fingerprint

Kynurenic Acid
Kynurenine
Pentylenetetrazole
kynurenine-oxoglutarate transaminase
Hippocampus
Ionotropic Glutamate Receptors
Excitatory Amino Acid Antagonists
Excitatory Postsynaptic Potentials
Glutamate Receptors
Brain
Neuroprotective Agents
Nervous System Diseases
Baths
Tryptophan
Anticonvulsants
Arginine
Epilepsy
In Vitro Techniques
Pharmacology
Pharmaceutical Preparations

Keywords

  • Epileptic seizure
  • Hippocampus
  • In vitro electrophysiology
  • Kynurenic acid
  • l-Kynurenine
  • Neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "The pentylenetetrazole-induced activity in the hippocampus can be inhibited by the conversion of l-kynurenine to kynurenic acid: An in vitro study",
abstract = "The kynurenine pathway converts tryptophan into various compounds, including l-kynurenine, which in turn can be converted into the excitatory amino acid receptor antagonist kynurenic acid. The ionotropic glutamate receptors have been considered to be attractive targets for new anticonvulsants in neurological disorders such as epileptic seizure. This study was designed to examine the conversion of l-kynurenine to kynurenic acid and to investigate the effects of kynurenic acid on pentylenetetrazole-treated rat brain slices, and in parallel to draw attention to the fact that a well-designed in vitro model has many advantages in pharmacological screening. Schaffer collateral stimulation-evoked field EPSPs were recorded from area CA1 of rat hippocampal slices in vitro; drugs were bath-applied. Pretreatment with the kynurenic acid precursor l-kynurenine led to the elimination of the effect of pentylenetetrazole on hippocampal slices in vitro. N-Omega-nitro-l-arginine, which inhibits kynurenine aminotransferase I and II, abolished this neuroprotective effect. This study has furnished the first in vitro electrophysiological evidence that rat brain slices have the enzymatic capacity to convert exogenously administered l-kynurenine (16 μM) to kynurenic acid in an amount sufficient to protect them against pentylenetetrazole (1 mM)-induced hyperexcitability.",
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AU - Nagy, David

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AU - Sas, K.

AU - Vécsei, L.

AU - Toldi, J.

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AB - The kynurenine pathway converts tryptophan into various compounds, including l-kynurenine, which in turn can be converted into the excitatory amino acid receptor antagonist kynurenic acid. The ionotropic glutamate receptors have been considered to be attractive targets for new anticonvulsants in neurological disorders such as epileptic seizure. This study was designed to examine the conversion of l-kynurenine to kynurenic acid and to investigate the effects of kynurenic acid on pentylenetetrazole-treated rat brain slices, and in parallel to draw attention to the fact that a well-designed in vitro model has many advantages in pharmacological screening. Schaffer collateral stimulation-evoked field EPSPs were recorded from area CA1 of rat hippocampal slices in vitro; drugs were bath-applied. Pretreatment with the kynurenic acid precursor l-kynurenine led to the elimination of the effect of pentylenetetrazole on hippocampal slices in vitro. N-Omega-nitro-l-arginine, which inhibits kynurenine aminotransferase I and II, abolished this neuroprotective effect. This study has furnished the first in vitro electrophysiological evidence that rat brain slices have the enzymatic capacity to convert exogenously administered l-kynurenine (16 μM) to kynurenic acid in an amount sufficient to protect them against pentylenetetrazole (1 mM)-induced hyperexcitability.

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