Ammonium Ion Inhibition of Evoked Release of Endogenous Glutamate From Hippocampal Slices

The effect of pathophysiological levels (2‐5 m m ) of ammonium chloride on the efflux of endogenous and exogenous [ 14 C]glutamate from hippocampal slices was studied. The evoked release of glutamate which occurs dring tissue depolarization with 56 m m ‐KCl was greatly reduced when the tissue had been exposed to NH 4 Cl for 40–80 min. This effect was seen whether or not glutamine (0.5 m m ) was present in the incubation medium. The effect was completely reversible. The spontaneous efflux and the evoked release of [ 14 C]glutamate was, on the contrary, completely unaltered after exposure of the slice to ammonium ions. Nigher (20–36 m m ) amounts of NH 4 Cl evoked a release of [ 14 C]glutamate from the crude mitochondrial fraction, as did high concentrations of KCl. The results are discussed in relation to the compartmentation of glutamate metabolism and the pathogenesis of hepatic coma.