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Functional Comparison of d ‐Serine and Glycine in Rodents: The Effect on Cloned NMDA Receptors and the Extracellular Concentration
Author(s) -
Matsui Takaaki,
Sekiguchi Masayuki,
Hashimoto Atsushi,
Tomita Urara,
Nishikawa Toru,
Wada Keiji
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65010454.x
Subject(s) - nmda receptor , extracellular , receptor , glycine , biology , microdialysis , serine , biochemistry , chemistry , amino acid , microbiology and biotechnology , pharmacology , enzyme
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 ED 50 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 ED 50 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 µ M ) 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.