Presence of the N-methyl-D-aspartate-associated glycine receptor agonist, D-serine, in human temporal cortex: comparison of normal, Parkinson, and Alzheimer tissues.

The amino acid D-serine (D-Ser), previously recognized as a pharmacological tool for potentiating neuronal activity mediated by the N-methyl-D-aspartate (NMDA) receptor complex, in vitro and in vivo, has been observed in several brain regions of the rat and mouse, most prominently in cortex. In addition to reconfirming the presence and distribution of D-Ser in rat brain, we have observed, for the first time, endogenous, free D-Ser in temporal cortex of normal human brains at a level of 2.18 +/- 0.12 nmol/mg of protein, representing 15 +/- 2% of the free L-Ser pool. The D- and L-Ser specific content and the D/L-Ser ratio obtained from temporal cortex of Parkinson and Alzheimer brains did not differ significantly from those of controls. However, at the levels observed here, and considering its specificity and affinity for the NMDA-associated glycine receptor, endogenous D-Ser is a plausible NMDA receptor glycine site agonist.