title: Hydroxyl radicals release in rat striatum involves metabotropic glutamate receptors.
abstract: Disruption of glutamate homeostasis frequently leads to oxidative stress and to the release of hydroxyl radicals (radical OH). Here, we investigated, via a microdialysis approach, the possible involvement of metabotropic glutamate receptors in the glutamate-induced release of hydroxyl radicals in adult rat striatum. Glutamate was applied at low amount, resulting in a moderate release that was not inhibited by dizocilpine (MK-801), a specific NMDA receptor antagonist. (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a broad spectrum metabotropic antagonist, that does not exert any effect on the basal release of radical OH suppressed their response to glutamate. (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD), a non-selective metabotropic glutamate receptors agonist, promoted an radical OH release almost similar to that observed after glutamate, which was similarly impaired by co-infusion with MCPG. By contrast, infusion of (RS)-3,5-dihydroxyphenylglycine (DHPG), a more specific group I metabotropic glutamate receptors agonist, did not result in any appreciable radical OH response. Thus, beside NMDA receptors, some metabotropic glutamate receptors may also be involved in the glutamate-induced release of hydroxyl radicals.
authors.affiliation: Medicinal Chemistry Laboratory, CRBM, CNRS UPR 1086, ENSCM, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Laplanche
authors.forename: Martine
authors.initials: M
authors.lastname: Michaud
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kamenka
authors.forename: Gérard
authors.initials: G
authors.lastname: Barbanel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C474696:methyl-(4-carboxyphenyl)glycine; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D017665:Hydroxyl Radical; D018698:Glutamic Acid; D008734:Methoxyhydroxyphenylglycol; D016291:Dizocilpine Maleate; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol