Glutamine enhances glutamate release in preference to γ-aminobutyrate release in hippocampal slices

To see the effect of physiological concentrations of glutamine on glutamate and gamma-aminobutyrate (GABA) release, rat hippocampal slices were incubated and (or) superfused without or with 0.25 mM glutamine in the presence or absence of Ca2+. The spontaneous and high K+-evoked release of glutamine, glutamate, and GABA was measured by precolumn derivatization and reversed phase high performance liquid chromatography. The spontaneous release of glutamate was increased by superfusion with glutamine and this increase was three times greater in the absence than in the presence of Ca2+. Spontaneous GABA release was not increased by glutamine. While in the absence of glutamine, the release of glutamate and GABA evoked by 50 mM K+ was about equal, in the presence of glutamine the evoked release of glutamate was nearly three times greater than that of GABA. The large evoked release of glutamate in the presence of glutamine was Ca2+ dependent nearly to the same extent as the smaller evoked release in the absence of glutamine. Results suggest that the availability of extracellular glutamine regulates the release of glutamate but not of GABA. Extracellular Ca2+ controls the spontaneous conversion of glutamine to glutamate but the site and mechanism of this control is uncertain.