CORRELATION OF IN-VIVO NITRIC-OXIDE AND CGMP WITH GLUTAMATE GLUTAMINEMETABOLISM IN THE RAT STRIATUM/

We have examined how the suppression of endogenous production of nitri c 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 am ino acid release, an in vivo assay system for extracellular nitrite (N O2-) and amino acids was employed using an in vivo microdialysis techn ique. An NO synthase inhibitor (N-G-nitro-L-arginine methyl ester, L-N AME) in concentrations ranging between 4-40 mM was perfused into the r at 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 prod uction 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-bro mo-cGMP showed a tendency to decrease GLN. In conclusion, striatal GLU /GLN metabolism is a function of the tissue concentration of NO. Norma l endogenous concentration of NO causes GLU to be released at a consis tent basal level, and enhanced tissue NO production facilitates GLU re lease via pathways including cGMP formation. We hypothesize that NO ma y suppress GLN formation by astrocytes.