β-alanine release from the adult and developing hippocampus is enhanced by ionotropic glutamate receptor agonists and cell-damaging conditions

The release of the inhibitory amino acid p-alanine was investigated in hippocampal slices from adult (3-month-old) and developing (7-day-old) mice, using a superfusion system. The release was enhanced by p-alanine itself and the structural analogs taurine and gamma-aminobutyrate. It was dependent on Na+, but independent of Ca2+ in both mature and immature hippocampus, being thus mostly mediated by uptake carriers operating in an outward direction. The release was potentiated in the developing mice, but not affected in the adults, by the ionotropic glutamate receptor agonists N-methyl-D-aspartate, kainate, 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and tetrazolylglycine in a receptor-mediated manner. Cell-damaging conditions, including hypoxia, hypoglycemia, ischemia, oxidative stress and the presence of free radicals, greatly enhanced p-alanine release at both ages, but more markedly in the adults. The great amounts of p-alanine, together with the inhibitory amino acids taurine and gamma-aminobutyrate, released simultaneously with the excitatory amino acids in the hippocampus may constitute an important protective mechanism against excitotoxicity, which leads to neuronal death.