D-Amino Acids as Putative Neurotransmitters: Focus on D-Serine |
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Authors: | Snyder Solomon H. Kim Paul M. |
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Affiliation: | (1) School of Medicine Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, The Johns Hopkins University, 725 N. Wolfe Street, Baltimore, MD, 21205 |
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Abstract: | Of the twenty amino acids in the mammalian body, only serine and aspartate occur in D-configuration as well as L-configuration in significant amount. D-serine is selectively concentrated in the brain, localized to protoplasmic astrocytes that ensheath synapses and distributed similarly to N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. D-serine has been found to function as an endogenous ligand for the glycine site of the NMDA receptor. Evidences for this include the greater potency of D-serine to activate this site than glycine, and D-amino acid oxidase, which degrades D-serine as well as other neutral D-amino acids, markedly attenuates NMDA neurotransmission. D-serine is also formed by serine racemase, a recently cloned enzyme that converts L-serine to D-serine. Thus, in many ways D-serine fulfills criteria for defining its functionality as a neurotransmitter and challenges the dogma relating to neurotransmission, for it is the unnatural isomeric form of an amino acid derived from glia rather than neurons. |
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Keywords: | D-serine D-aspartate astrocytes N-methyl-D-aspartate (NMDA) receptor Bergmann glia |
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