title: Glutamate inhibition of NMDA-induced hydroxyl radical release: an ontogenic study in rat.
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.
authors: CRBM, CNRS UPR 1086, Medicinal Chemistry Laboratory, ENSCM, 8, rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
authors: G
authors: G
authors: Cambonie
authors: J M
authors: JM
authors: Kamenka
authors: G
authors: G
authors: Barbanel
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D012118:Resorcinols; D012459:Salicylates; D017665:Hydroxyl Radical; D018698:Glutamic Acid; C079215:3,5-dihydroxyphenylglycine; D016202:N-Methylaspartate; D005998:Glycine