nitroarginine and fluorocitrate

The role of glial cells in nitric oxide production in the cerebellum of conscious rats was investigated with a glial selective metabolic inhibitor, fluorocitrate. The levels of nitric oxide metabolites (nitrite plus nitrate) in the dialysate following in vivo microdialysis progressively increased to more than 2-fold the basal levels during a 2-h infusion of fluorocitrate (1 mM), and the increase persisted for more than 2 h after the treatment. Pretreatment with N(G)-nitro-L-arginine methyl ester attenuated the fluorocitrate-induced increase in nitric oxide metabolite levels. None of the glutamate receptor antagonists, including D(-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione, and (+/-)-alpha-methyl-4-carboxyphenylglycine, inhibited the fluorocitrate-induced increase. The L-arginine-induced increase was significantly reduced by fluorocitrate treatment, while N-methyl-D-aspartate, (+)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and trans-(+/-)-1-amino-(1S,3R)-cyclopentane-dicarboxylic acid increased nitric oxide metabolites levels in the fluorocitrate-treated rats, as much as in control animals. These results suggest that glial cells play an important role in modulating nitric oxide production in the cerebellum by regulating L-arginine availability.

Topics: Aconitate Hydratase; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Behavior, Animal; Benzoates; Cerebellum; Citrates; Citric Acid Cycle; Cycloleucine; Enzyme Inhibitors; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Extracellular Space; Glycine; Male; N-Methylaspartate; Neuroglia; Neuroprotective Agents; NG-Nitroarginine Methyl Ester; Nitrates; Nitric Oxide; Nitrites; Nitroarginine; Quinoxalines; Rats; Rats, Wistar; Substrate Specificity