Hydroxyl radicals release in rat striatum involves metabotropic glutamate receptors.
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.
Laplanche
Loïc
L
Medicinal Chemistry Laboratory, CRBM, CNRS UPR 1086, ENSCM, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
Michaud
Martine
M
Kamenka
Jean-Marc
JM
Barbanel
Gérard
G
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
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