Inhibitory effects of ammonium ions and some amino acids on stimulated brain respiration and cerebral amino acid transport

Abstract

Ammonium ions cause a suppression of the respiratory response of rat brain cortex slices to electrical stimulation and this is partly reversed by the addition of DL-methionine sulfoxide or L-glutamine but not by addition of L-glutamate or DL-α-methylglutamate. Other basic ions, e.g. tetramethylammonium, pyridine, or pyrimidine, at equivalent concentrations are without effect. Ammonium ions have less inhibitory effect on the respiratory response to high potassium ion concentrations than on that due to application of electrical impulses. They also bring about a marked suppression of the rate of glycine uptake into rat brain cortex slices, the effect being much greater with electrically stimulated brain than with unstimulated brain. Methionine sulfoxide diminishes this suppressive effect. They exercise relatively small inhibitory effects on the depressed rate of glycine uptake obtained in the presence of high potassium ion concentrations. The effect of ammonium ions is considered to be partly due to the fall in cell ATP brought about by the operation of glutamine synthetase. The results are consistent with the view that the extent of stimulation of brain respiration due to electrical impulses or to increased concentration of potassium ions is dependent on the cell level of ATP. L-Glutamate, L-glutamine, or γ-aminobutyrate diminishes the suppressive effects of ammonium ions on glycine influx into brain. L-Glutamate, moreover, diminishes the stimulatory effects of electrical stimulation on brain respiration, lesser effects being produced by L-glutamine or γ-aminobutyrate.