HETEROCARRIER-MEDIATED RECIPROCAL MODULATION OF GLUTAMATE AND GLYCINE RELEASE IN RAT CEREBRAL-CORTEX AND SPINAL-CORD SYNAPTOSOMES

The effects of glutamic acid (Glu) and glycine (Gly) on each others release were studied using rat brain cortex and spinal cord synaptosomes. Previously taken up [H-3] Gly and [H-3] D-aspartic acid ([H-3] D-Asp) was employed as markers for Gly and Glu/Asp release, respectively. Glu enhanced the release of [H-3] Gly (EC(50) = 8.4 mu M) from cortical synaptosomes. The effect of Glu was not mimicked by the glutamate receptor agonists N-methyl-D-aspartic acid (NMDA), kainic or quisqualic acid. The Glu effect was abolished by the Glu/Asp uptake inhibitor D-threo-hydroxy-aspartic acid and it was Na+ sensitive. D-Asp also increased [H-3] Gly release (EC(50) = 9.9 mu M) and the effect was blocked by the Glu/Asp uptake inhibitor. In contrast to its effect in the cortex, Glu failed to increase the release of [H-3] Gly from spinal cord synaptosomes. Gly enhanced the outflow of [H-3] D-Asp from rat cerebral cortex and spinal cord synaptosomes (EC(50) = 75.0 and 99.5 mu M, respectively). Gly was much more potent a releaser of [H-3] D-Asp in the spinal cord than in the cortex. The Gly effects were insensitive to strychnine or to 7-Cl-kynurenic acid, antagonists at the two known Gly receptors, but they were strongly Na+ dependent. Our results are compatible with the idea that high-affinity uptake systems specific for Glu/Asp or Gly are colocalized on the same nerve terminal in rat spinal cord and cerebral cortex. Activation of the Glu/Asp heterocarrier sited on glycinergic terminals may promote the release of Gly, at least in brain cortex, while activation of the Gly heterocarrier sited on Glu/Asp nerve terminals may lead to excitatory amino acid release.