Correlation of in vivo nitric oxide and cGMP with glutamate/glutamine metabolism in the rat striatum

Kouichi Ohta, Nobuo Araki, Mamoru Shibata, Junichi Hamada, Satoru Komatsumoto, Kunio Shimazu, Yasuo Fukuuchi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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 (N(G)-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.

Original languageEnglish
Pages (from-to)379-384
Number of pages6
JournalNeuroscience Research
Issue number4
Publication statusPublished - 1996 Aug


  • 8-bromoguanosine 3':5'-cyclic monophosphate
  • Excitatory amino acid
  • Glutamine synthase
  • Hydroxylamine
  • In vivo microdialysis
  • N(G)-nitro-L-arginine methyl ester
  • Neurotransmitter
  • Nitric oxide synthase

ASJC Scopus subject areas

  • General Neuroscience


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