Heterocarrier-mediated reciprocal modulation of glutamate and glycine release in rat cerebral cortex and spinal cord synaptosomes

Abstract

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 [ 3H]Gly and [ 3H] d-aspartic acid ([ 3H] d-Asp) was employed as markers for Gly and Glu/Asp release, respectively. Glu enhanced the release of [ 3 H] Gly ( EC 50 = 8.4 μ 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 [ 3H]Gly release (EC 50 = 9.9 μM) 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 [ 3H]Gly from spinal cord synaptosomes. Gly enhanced the outflow of [ 3H] d-Asp from rat cerebral cortex and spinal cord synaptosomes (EC 50 = 75.0 and 99.5 μM, respectively). Gly was much more potent a releaser of [ 3H] 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.