High concentrations of neutral amino acids activate NMDA receptor currents in rat hippocampal neurons

John R. Pace; Martin Brian; Steven M. Paul; Michael A. Rogawski

doi:10.1016/0304-3940(92)90343-6

High concentrations of neutral amino acids activate NMDA receptor currents in rat hippocampal neurons

John R. Pace, Martin Brian, Steven M. Paul, Michael A. Rogawski

Washington University School of Medicine

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

High concentrations (30 μM-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 μM glycine and 1 μM 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 μM) and completely blocked by the competitive N-methyl-d-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (30 μM). 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.

Original language	English
Pages (from-to)	97-100
Number of pages	4
Journal	Neuroscience Letters
Volume	141
Issue number	1
DOIs	https://doi.org/10.1016/0304-3940(92)90343-6
State	Published - Jul 6 1992

Keywords

Alanine
Cysteine
Glycine
Hippocampal neuron
N-Methyl-d-aspartate receptor
Proline
Serine

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title = "High concentrations of neutral amino acids activate NMDA receptor currents in rat hippocampal neurons",

abstract = "High concentrations (30 μM-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 μM glycine and 1 μM 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 μM) and completely blocked by the competitive N-methyl-d-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (30 μM). 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.",

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AU - Pace, John R.

AU - Brian, Martin

AU - Paul, Steven M.

AU - Rogawski, Michael A.

PY - 1992/7/6

Y1 - 1992/7/6

N2 - High concentrations (30 μM-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 μM glycine and 1 μM 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 μM) and completely blocked by the competitive N-methyl-d-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (30 μM). 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.

AB - High concentrations (30 μM-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 μM glycine and 1 μM 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 μM) and completely blocked by the competitive N-methyl-d-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (30 μM). 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.

KW - Alanine

KW - Cysteine

KW - Glycine

KW - Hippocampal neuron

KW - N-Methyl-d-aspartate receptor

KW - Proline

KW - Serine

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AN - SCOPUS:0026748210

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VL - 141

SP - 97

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JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 1

ER -

High concentrations of neutral amino acids activate NMDA receptor currents in rat hippocampal neurons

Abstract

Keywords

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