A microdialysis study investigating the mechanisms of hydroxyl radical formation in rat striatum exposed to glutamate.
Considerable evidence has linked hydroxyl radicals (.OH) to excitotoxicity. Glutamate infused through a microdialysis probe into rat striatum induced a massive .OH production, which was completely blocked by PBN and attenuated by dizocilpine, 2-amino-5-phosphonopentanoic acid (AP-5), NG-nitro-L-arginine methyl ester (L-NAME) and mepacrine. Thus, we suggest that the neurotoxic effects of glutamate in vivo may derive from an increased formation of .OH resulting from excessive activation of NMDA receptors and downstream enzymes such as NOS and PLA2.
Lancelot
E
E
Laboratoire de Pharmacologie, Université René Descartes, Paris, France.
Revaud
M L
ML
Boulu
R G
RG
Plotkine
M
M
Callebert
J
J
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003497:Cyclic N-Oxides; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism; D009589:Nitrogen Oxides / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D007502:Iron Chelating Agents; D009498:Neurotoxins; D009589:Nitrogen Oxides; D017665:Hydroxyl Radical; C029217:phenyl-N-tert-butylnitrone; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C009135:2,3-dihydroxybenzoic acid; D015763:2-Amino-5-phosphonovalerate; D011796:Quinacrine; D019331:NG-Nitroarginine Methyl Ester