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

The effects of glutamic acid (Glu) and glycine (Gly) on each others re lease 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. G lu 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 rec eptor agonists N-methyl-D-aspartic acid (NMDA), kainic or quisqualic a cid. The Glu effect was abolished by the Glu/Asp uptake inhibitor D-th reo-hydroxy-aspartic acid and it was Na+ sensitive. D-Asp also increas ed [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 syn aptosomes. Gly enhanced the outflow of [H-3] D-Asp from rat cerebral c ortex and spinal cord synaptosomes (EC(50) = 75.0 and 99.5 mu M, respe ctively). Gly was much more potent a releaser of [H-3] D-Asp in the sp inal cord than in the cortex. The Gly effects were insensitive to stry chnine or to 7-Cl-kynurenic acid, antagonists at the two known Gly rec eptors, but they were strongly Na+ dependent. Our results are compatib le with the idea that high-affinity uptake systems specific for Glu/As p 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 bra in cortex, while activation of the Gly heterocarrier sited on Glu/Asp nerve terminals may lead to excitatory amino acid release.