Glycine action on N-methyl-D-aspartate receptors in rat hippocampal neurons

The modulatory effect of glycine and other amino acids on the activity of N-methyl-D-aspartate (NMDA) receptors has been investigated using a concentration clamp method in the acutely isolated pyramidal neurons from rat hippocampus. The dose-response curves for L-aspartate, measured on the background of several glycine concentrations, were close to Langmuir isotherms with Kd values practically independent of the concentration of glycine. The facilitatory action of glycine appeared at concentrations below 0.1 microM and saturated between 10 and 100 microM. This effect demonstrated marked densensitization, at least at concentrations higher than 5 microM. Facilitation of the responses was shared by amino acids with the potencies diminishing as follows: glycine, D-serine, D-alanine greater than L-proline, D-proline, hydroxy-L-proline, taurine greater than L-alanine, L-serine. This sequence did not correlate with the ability of these amino acids to activate strychnine-sensitive glycine receptors.