Functional comparison of D-serine and glycine in rodents: the effect on cloned NMDA receptors and the extracellular concentration

J Neurochem. 1995 Jul;65(1):454-8. doi: 10.1046/j.1471-4159.1995.65010454.x.


We compared the activity of free D-Ser on the potentiation of cloned NMDA receptors with that of Gly by using a Xenopus oocyte expression system. The extracellular concentration of free D-Ser and Gly was further studied by means of microdialysis. The ED50 values of D-Ser were three to four times lower than those of Gly in any combination of epsilon 1, epsilon 2, epsilon 3, or epsilon 4 and zeta 1. Site-directed mutagenesis of zeta 1 subunits revealed that some aromatic residues necessary for the action of Gly affected the ED50 value of D-Ser. This result showed that the residues play crucial roles in the action of D-Ser. In vivo microdialysis of rodent brain revealed that the extracellular concentration of free D-Ser in the frontal cortex (6.5 microM) was high enough to saturate the Gly site on the NMDA receptor, but that in the cerebellum was not. These findings suggest that D-Ser is a candidate of the endogenous potentiator of the NMDA receptor in the rodent frontal cortex.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cloning, Molecular
  • Electrophysiology
  • Extracellular Space / metabolism*
  • Glycine / physiology*
  • Male
  • Microdialysis
  • Mutagenesis, Site-Directed
  • Oocytes
  • Osmolar Concentration
  • Rats / physiology*
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Serine / physiology*
  • Xenopus laevis


  • Receptors, N-Methyl-D-Aspartate
  • Serine
  • Glycine