2000/04/25 by Jean‐Pierre Mothet, Angèle Parent, Herman Wolosker +5 · 2 citations
Biochemistry, Genetics and Molecular Biology · Neuroscience · Chemistry · #Amino Acid Enzymes and Metabolism #Neuroscience and Neuropharmacology Research #Molecular Sensors and Ion Detection #NMDA receptor #Glycine #Serine #Receptor #Biochemistry #Glutamate receptor #Agonist #Endogeny #Biology #Chemistry #Amino acid #Enzyme
paper · pdf · doi:10.1073/pnas.97.9.4926
openalex publication_date 2000/04/25 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/06
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.