Functional comparison of D-serine and glycine in rodents: the effect on cloned NMDA receptors and the extracellular concentration.
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.
Matsui
T
T
Department of Degenerative Neurological Diseases, National Center of Neurology and Psychiatry, Tokyo, Japan.
Sekiguchi
M
M
Hashimoto
A
A
Tomita
U
U
Nishikawa
T
T
Wada
K
K
D000818:Animals; D003001:Cloning, Molecular; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism*; D005998:Glycine / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D016297:Mutagenesis, Site-Directed; D009865:Oocytes; D009994:Osmolar Concentration; D051381:Rats / Q000502:physiology*; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D012694:Serine / Q000502:physiology*; D014982:Xenopus laevis
D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D005998:Glycine