NMDA-induced hippocampal [ 3H]norepinephrine release is modulated by glycine

Abstract

Kynurenic acid (KYN) non-competitively inhibited N-methyl-D-aspartate (NMDA)-induced [ 3H]norepinephrine ([ 3H]NE) release from rat hippocampal slices. At 100 μM KYN, the effect on release was primarily on the maximal obtainable response to NMDA. Glycine was able to completely block the inhibitory effects of 100 μM KYN on NMDA-evoked release. This ability to prevent KYN inhibition of release was shared by other amino acids with the following order of potency: glycine > D-serine > D-alanine ⪢ L-serine ⩾ L-alanine. Neither isomer of valine or threonine was able to reverse KYN inhibition of NMDA-induced release. These potencies agreed with the relative abilities of these amino acids to displace stychnine-insensitive [ 3H]glycine binding to rat brain membranes. Glycine and D-serine had no effect on the inhibition of NMDA-stimulated [ 3H]NE release produced by D-2-amino-5-phosphonovaleric acid, MK-801 or Mg 2+. Also, neither amino acid modified KYN inhibition of kainic acid-induced release. These data demonstrate that the glycine regulatory site associated with the NMDA receptor can be demonstrated in whole brain slices by using an antagonist to attenuate the influences of endogenous glycine.