Glutamate inhibition of NMDA-induced hydroxyl radical release: an ontogenic study in rat.
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.
Cambonie
G
G
CRBM, CNRS UPR 1086, Medicinal Chemistry Laboratory, ENSCM, 8, rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
Kamenka
J M
JM
Barbanel
G
G
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
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