Endogenous <scp>d</scp>‐Serine in Rat Brain: <i>N</i>‐Methyl‐<scp>d</scp>‐Aspartate Receptor‐Related Distribution and Aging

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<jats:p><jats:bold>Abstract: </jats:bold> Recently, a substantial amount of free <jats:sc>d</jats:sc>‐serine has been demonstrated in rat brain, although it has long been presumed that <jats:sc>d</jats:sc>‐amino acids are uncommon in mammals. The anatomical distribution and age‐related changes in endogenous <jats:sc>d</jats:sc>‐serine have been examined here to obtain insight into its physiological functions. Free <jats:sc>d</jats:sc>‐serine exclusively occurs in brains, with a persistent high content from birth to at least 86 postnatal weeks. The patterns of the regional variations and the postnatal changes in brain <jats:sc>d</jats:sc>‐serine are closely correlated with those of the <jats:italic>N</jats:italic>‐methyl‐<jats:sc>d</jats:sc>‐aspartate (NMDA)‐type excitatory amino acid receptor. Because <jats:sc>d</jats:sc>‐serine potentiates NMDA receptor‐mediated transmission by selective stimulation of the strychnine‐insensitive glycine site of the NMDA receptor, it is proposed that <jats:sc>d</jats:sc>‐serine is a novel candidate as an intrinsic ligand for the glycine site in mammalian brain.</jats:p>

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