Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Mothet JP,Parent AT,Wolosker H,Brady RO Jr,Linden DJ,Ferris CD,Rogawski MA,Snyder SHdoi
10.1073/pnas.97.9.4926keywords:
subject
Has Abstractpub_date
2000-04-25 00:00:00pages
4926-31issue
9eissn
0027-8424issn
1091-6490pii
97/9/4926journal_volume
97pub_type
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