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
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Buffers
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Entorhinal Cortex / drug effects
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Entorhinal Cortex / metabolism
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Entorhinal Cortex / physiopathology
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Epilepsy / chemically induced
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Epilepsy / drug therapy
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Evoked Potentials / drug effects
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Excitatory Amino Acid Antagonists / metabolism*
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Excitatory Amino Acid Antagonists / pharmacology*
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Glycine / metabolism
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Hippocampus / drug effects
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Hippocampus / metabolism
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Hippocampus / physiopathology
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Kynurenic Acid / metabolism*
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Kynurenic Acid / pharmacology*
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Magnesium / pharmacology
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Male
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Neurotransmitter Agents / metabolism
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Neurotransmitter Agents / pharmacology
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Organ Culture Techniques
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / antagonists & inhibitors*
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Tryptophan / metabolism
Substances
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Buffers
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Excitatory Amino Acid Antagonists
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Neurotransmitter Agents
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Tryptophan
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Kynurenic Acid
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Magnesium
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Glycine