Paper
D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor.
Published Apr 25, 2000 · J. Mothet, A. Parent, Herman Wolosker
Proceedings of the National Academy of Sciences of the United States of America
1,107
Citations
47
Influential Citations
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.
In Vitro Study
Highly CitedD-serine is an endogenous modulator of the glycine site of NMDA receptors, and its selective degradation with D-amino acid oxidase significantly reduces NMDA receptor-mediated neurotransmission.
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