Control of glutaminase activity in rat brain cortex in vitro: influence of glutamate, phosphate, ammonium, calcium and hydrogen ions.

Studies of the kinetics of product inhibitions of glutaminase activity of rat brain cortical homogenates incubated in Krebs-Ringer medium in presence of the activating anion phosphate show that whereas ammonium acts competitively with respect to L-glutamine, L-glutamate acts non-competitively. Calcium ions are stimulatory with maximum stimulation occurring at 1 mM. This effect is blocked by EGTA. The optimum pH for glutamine hydrolysis is 8.2 with maximum stimulation by Ca2+ occurring at pH 7.8. Similar observations have been made with a crude synaptosomal fraction of brain cortex and also with brain cortex slices where the rates of hydrolyses are about one order of magnitude lower than those with brain homogenates. Ammonium (2 mM) diminishes glutamate and aspartate, and enhances glutamine and ammonium levels of brain cortex slices incubated in a physiological glucose-saline medium. It is suggested that stimulation by Ca2+ ions may occur in part by enhanced phosphate, and by diminished glutamate and H+ ion concentrations of mitochondria and that mutual regulation of glutaminase and glutamine synthetase may exist in glia but not in nerve terminals. It is proposed that calcium plays a role in maintaining normal electrical activities of certain neurons in part by its effects on glutamate regeneration in nerve terminals from glial-derived glutamine and that when brain cell ammonium is maintained at levels above the normal, suppressions of glutaminase activity in nerve terminals could affect the rate of formation of glutamine-derived neurotransmitters.