D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor

Jean Pierre Mothet, Angèle T. Parent, Herman Wolosker, Roscoe O. Brady, David J. Linden, Christopher D. Ferris, Michael A. Rogawski, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

878 Scopus citations


Functional activity of N-methyl-D-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although D-serine is a more potent agonist. Localizations of D-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than glycine. We now show that selective degradation of D-serine with D-amino acid oxidase greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMDA receptor-mediated calcium flux. The inhibitory effects of the enzyme are fully reversed by exogenously applied D-serine, which by itself did not potentiate NMDA receptor-mediated synaptic responses. Thus, D-serine is an endogenous modulator of the glycine site of NMDA receptors and fully occupies this site at some functional synapses.

Original languageEnglish (US)
Pages (from-to)4926-4931
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - Apr 25 2000

ASJC Scopus subject areas

  • General


Dive into the research topics of 'D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor'. Together they form a unique fingerprint.

Cite this