Effect of Glutamine on Glutamate Release from Hippocampal Slices Induced by High K⁺ or by Electrical Stimulation: Interaction with Different Ca²⁺ Concentrations

Abstract

To characterize the effect of glutamine on the release of glutamate, aspartate, and gamma-aminobutyric acid (GABA), rat hippocampal slices were superfused with different concentrations of glutamine or Ca2+. Amino acids released and retained were analyzed by HPLC. Glutamine (0.5 mmol/L) increased more than threefold the release of glutamate evoked by 50 mmol/L K+ in the presence of 2.6 mmol/L Ca2+ without a corresponding increase in glutamate content, while the release of aspartate was increased less and that of GABA not at all by glutamine. The evoked release of all three amino acids, including the enhanced release of glutamate in the presence of glutamine, was strongly dependent on Ca2+ concentrations between 0.1 and 2.6 mmol/L. The potentiation of glutamate release by glutamine reached a plateau at 0.25 mmol/L glutamine. Intermittent electrical field stimulation increased the release of only glutamate and this release was nearly doubled by glutamine. The increased release was Ca2+ dependent and tetrodotoxin (TTX) sensitive. Results suggest that extracellular glutamine promotes primarily the formation of releasable glutamate and this enhancement is dependent on extracellular Ca2+.

Ammonia-induced taurine release from cultured rabbit m�ller cells is an osmoresistant process mediated by intracellular accumulation of cyclic AMP

“…The lowest ammonia concentration found to induce cAMP accumulation and Tau release in cultured Muller glia (0.25 mM) is close to that measured in lightactivated bee retina (Tsacopoulos and Poitry, 1995). Transient rises in ammonia concentration have also been measured in brain slices (Szerb and O'Regan, 1985) or synaptosomes under conditions simulating active neurotransmission (Erecinska et al, 1990). It is thus tempting to assume that in retina, ammonia is an actual signal molecule transmitted from neurons (photoreceptors) to glial cells to synchronize some of the functions of the two cell types: Ammonia released from activated photoreceptors would induce cAMP accumulation in the adjacent Muller cells, resulting in Tau release.…”

SAT1, a glutamine transporter, is preferentially expressed in GABAergic neurons

“…This mechanistic view is supported by glutamine being preferentially metabolized to the transmitter pools of glutamate and GABA (Ward et al, 1983; Battaglioli and Martin, 1990; Sonnewald et al, 1993) in order to maintain increased neuronal activity (Szerb and O'Regan, 1985; Storm-Mathisen et al, 1986; Verderio et al, 1999; Holten and Gundersen, 2008). Furthermore, glutamine synthetase, the key enzyme catalyzing the formation of glutamine from glutamate, is localized to perisynaptic astroglial processes (Martínez-Hernandez et al, 1977), whereas phosphate-activated glutaminase (PAG) catalyzing regeneration of glutamate from glutamine is enriched in nerve terminals (Kvamme, 1983; Laake et al, 1999).…”

The relationship between cytoplasmic free Ca2+ and the release of glutamate from synaptosomes

“…t o equilibrate with the bulk cytoplasm 141. The close physical proximity between the 'exocytotic' Ca" channels at the active zone and the exocytotic trigger further implies that the 'trigger' will be exposed to the high local concentration of Ca?+ in the vicinity of the channel mouth 14,191 If this model is correct. the fura 2 signal observed in synaptosomal populations represents predominantly the overflow of Ca" into the bulk cytoplasm.…”