Abstract
Hydroxyl radicals (.OH) are frequently associated with glutamate excitotoxicity and may be critical in the occurrence of perinatal brain damage. We thus investigated the mechanisms regulating the glutamate-induced release of toxic.OH during development, using microdialysis and salicylate as an.OH trap. Glutamate inhibited.OH release until post-natal day 14, but stimulated this release from day 21 onwards. DHPG [(RS)-3,5-dihydroxyphenylglycine], a group-I metabotropic glutamate receptor agonist, similarly reduced the.OH release at day 14, but was ineffective afterwards. DHPG also completely blunted the tremendous NMDA-induced.OH release at day 14 but not at day 21. Glutamate itself therefore tonically inhibited a possible free radical release through NMDA channel activation during early development.
MeSH terms
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Aging / drug effects
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Aging / physiology
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Animals
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Animals, Newborn / growth & development*
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Animals, Newborn / metabolism
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Brain / drug effects
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Brain / growth & development*
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Brain / metabolism*
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Glutamic Acid / metabolism*
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Glutamic Acid / pharmacology
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Glycine / analogs & derivatives
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Glycine / pharmacology
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Hydroxyl Radical / metabolism*
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Microdialysis
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N-Methylaspartate / pharmacology
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Neurons / drug effects
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Neurons / metabolism*
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Neurotoxins / metabolism
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Neurotoxins / pharmacology
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Oxidative Stress / physiology
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Rats
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Rats, Wistar
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Receptors, Metabotropic Glutamate / agonists
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Receptors, Metabotropic Glutamate / metabolism
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Resorcinols / pharmacology
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Salicylates / pharmacology
Substances
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Neurotoxins
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Receptors, Metabotropic Glutamate
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Receptors, N-Methyl-D-Aspartate
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Resorcinols
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Salicylates
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Hydroxyl Radical
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Glutamic Acid
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3,5-dihydroxyphenylglycine
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N-Methylaspartate
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Glycine