Changes in extracellular nitrite and nitrate levels after inhibition of glial metabolism with fluorocitrate

Abstract

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 (±)- α-methyl-4-carboxyphenylglycine, inhibited the fluorocitrate-induced increase. The l-arginine-induced increase was significantly reduced by fluorocitrate treatment, while N-methyl- d-aspartate, (+)- α-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.