Regulation of glutamate biosynthesis and release in vitro by low levels of ammonium ions

The content and release of endogenous amino acids from isolated rat hippocampal slices were measured. The tissue was perfused with control media and pulsed with high potassium media in order to induce synaptic release. Pathophysiological concentrations of ammonium ions (3--5 mM) were added to the control medium for 60 min prior to the induced release. Amino acids belonging to the putative transmitter group were released extensively during potassium perfusion and, except for glutamate, even after ammonium ion perfusion. The spontaneous secretion of glutamate increased, however, slowly after the addition of ammonia. The incorporation of 14C from radiolabelled glucose and acetate into the amino acid fraction was studied in the presence of ammonia-containing media. Glucose was utilized to a moderately increasing extent, but acetate-derived radioactivity was strikingly decreased in the amino acid fraction during ammonia perfusion. The decreased acetate incorporation into amino acids was mainly due to an inhibition by ammonia of the accumulation of acetate by the CNS tissue.