Beta-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 beta-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 beta-alanine itself and the structural analogs taurine and y-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 beta-alanine release at both ages, but more markedly in the adults. The great amounts of beta-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.
Saransaari
P
P
Tampere Brain Research Center, University of Tampere Medical School, Finland. blpisa@uta.fi
Oja
S S
SS
D000818:Animals; D015687:Cell Hypoxia; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals; D005947:Glucose / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009584:Nitrogen / Q000008:administration & dosage; D018384:Oxidative Stress; D012964:Sodium / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D015091:beta-Alanine / Q000378:metabolism* / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D005609:Free Radicals; D015091:beta-Alanine; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D012964:Sodium; D005947:Glucose; D009584:Nitrogen; D007608:Kainic Acid