[Endogenous D-serine in mammalian brains].
It is well established that, like glycine and D-alanine, D-serine potentiates glutamate neurotransmission via the N-methyl-D-aspartate (NMDA) receptor by selective stimulation of its strychnine-insensitive glycine site and acts as a co-agonist of the glutamate receptor. D-Serine has been found to modify behavioral changes associated with higher brain functions such as memory, convulsion, anxiety, psychotomimetic-induced abnormal behavior and cerebellar ataxia. Interestingly, a substantial amount of free D-serine has been demonstrated in mammalian brains, although it has long been presumed that D-amino acids are uncommon in mammals. Free D-serine is predominantly concentrated in the brain with a persistent high content throughout life. The patterns of the regional variations and the postnatal changes in brain D-serine are closely correlated with those of the R2B subunit of the N-methyl-D-aspartate (NMDA) type excitatory amino acid receptor. Moreover, D-serine is released to the extracellular space and taken up into the brain homogenates, C6 glioma cells and primary culture of astrocytes of the rat cerebral cortex. Recently, the conversion of L-serine to its D-form by serine racemase has been suggested by in vivo and in vitro experiments. These data are consistent with the view that D-serine might be an intrinsic positive modulator of the brain NMDA receptor containing the R2B subunit and play a pivotal role in controlling behavioral expression in mammals.
Nishikawa
T
T
Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University, School of Medicine, Japan.
Yamamoto
N
N
Tsuchida
H
H
Umino
A
A
Kawaguchi
N
N
D000818:Animals; D001921:Brain / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006801:Humans; D019998:Racemases and Epimerases / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy; D012694:Serine / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D013132:Spinocerebellar Degenerations / Q000188:drug therapy; D009435:Synaptic Transmission; D000099300:Serine Racemase
D018698:Glutamic Acid; D005998:Glycine; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase