title: Correlation of in vivo nitric oxide and cGMP with glutamate/glutamine metabolism in the rat striatum.
abstract: We have examined how the suppression of endogenous production of nitric oxide (NO) in the striatal tissue affects release of glutamate (GLU) and glutamine (GLN) in pentobarbital-anesthetized male Sprague-Dawley rats. For the quantitative measurement of tissue NO production and amino acid release, an in vivo assay system for extracellular nitrite (NO2-) and amino acids was employed using an in vivo microdialysis technique. An NO synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) in concentrations ranging between 4-40 mM was perfused into the rat striatum using the assay system. Tissue NO production was found to be inversely proportional to the L-NAME concentration. L-NAME likewise decreased striatal levels of GLU and GLN. Furthermore, tissue NO production showed a positive correlation with GLU (R = 0.62, P < 0.02) and GLN (R = 0.86, P < 0.001) concentrations. Exogenous application of NO and cGMP by intrastriatal perfusion with 0.1-2.5 mM hydroxylamine and 0.4-10 mM 8-bromo-cGMP, respectively, increased striatal GLU release in a dose-related manner. Hydroxylamine reduced GLN release, and 8-bromo-cGMP showed a tendency to decrease GLN. In conclusion, striatal GLU/GLN metabolism is a function of the tissue concentration of NO. Normal endogenous concentration of NO causes GLU to be released at a consistent basal level, and enhanced tissue NO production facilitates GLU release via pathways including cGMP formation. We hypothesize that NO may suppress GLN formation by astrocytes.
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: N
authors.initials: N
authors.lastname: Araki
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.forename: J
authors.initials: J
authors.lastname: Hamada
authors.forename: S
authors.initials: S
authors.lastname: Komatsumoto
authors.forename: K
authors.initials: K
authors.lastname: Shimazu
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuuchi
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005973:Glutamine; D009569:Nitric Oxide; D018698:Glutamic Acid; D006152:Cyclic GMP