High concentrations of neutral amino acids activate NMDA receptor currents in rat hippocampal neurons.
High concentrations (30 microM-5 mM) of the neutral amino acids L-serine, L-cysteine, L-alanine, L-proline and glycine elicited inward current responses when applied to hippocampal neurons patch clamped at -60 mV in the presence of 1-10 microM glycine and 1 microM strychnine. The amplitude of the response to L-serine increased in a concentration-dependent fashion within the range 0.1-10 mM (EC50, 2.6 mM). L-Serine (1 mM) currents were attenuated by Mg2+ (100 microM) and completely blocked by the competitive N-methyl-D-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1- phosphonic acid (CPP) (30 microM). The CPP block could be overcome by raising the concentration of L-serine. We conclude that high concentrations of some neutral amino acids activate NMDA receptor-coupled ion channels by acting as agonists at the NMDA recognition site.
Pace
J R
JR
Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Martin
B M
BM
Paul
S M
SM
Rogawski
M A
MA
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012694:Serine / Q000494:pharmacology
D000596:Amino Acids; D010879:Piperazines; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D008274:Magnesium