Functional Comparison of d‐Serine and Glycine in Rodents: The Effect on Cloned NMDA Receptors and the Extracellular Concentration

T Matsui, M Sekiguchi, A Hashimoto… - Journal of …, 1995 - Wiley Online Library
T Matsui, M Sekiguchi, A Hashimoto, U Tomita, T Nishikawa, K Wada
Journal of neurochemistry, 1995Wiley Online Library
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 ε1, ε2, ε3, or ε4 and ζ1.
Site‐directed mutagenesis of ζ1 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 …
Abstract
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 ε1, ε2, ε3, or ε4 and ζ1. Site‐directed mutagenesis of ζ1 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 µM) 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.
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