Inhibition of hypoxia-induced [(3)H]glycine release from chicken retina by the glycine transporter type-1 (GlyT-1) inhibitors NFPS and Org-24461.

Chicken posterior eyecup lined by the retina were prepared, loaded with [(3)H]glycine and superfused in order to determine its release in various experimental conditions. Electrical field stimulation of the retina evoked [(3)H]glycine release with a voltage- and frequency-dependent manner and this release may be originated from glycinergic amacrine cell processes of the inner plexiform layer of the retina. Glycine released from an abundance of different amacrine cells may modulate retinal circuitry by activation of inhibitory glycine receptors and by acting as a coagonist on N-methyl-d-aspartate receptors on AII amacrine cells and retinal ganglion cells. The latter effect of glycine may be modulated by glycine transporter type-1. Cells with glycine transporter type-1 immunopositive staining were visualized in the inner nuclear layer and dens immunolabeling was also detected throughout the inner plexiform layer of chicken retina. Glycine and the substrate-type glycine transporter type-1 inhibitor sarcosine increased [(3)H]glycine release from glycinergic amacrine cells and/or glial cells by extrusion of glycine from cytoplasmic pools by homo- and heteroexchange mechanisms. Deprivation of oxygen and glucose from the buffer used for superfusion evoked a marked increase in [(3)H]glycine efflux, an effect probably due to reverse mode operation of glycine transporter type-1. The non-transportable glycine transporter type-1 inhibitors NFPS and Org-24461, which did not alter [(3)H]glycine efflux from isolated chicken retina by themselves in normoxic condition, inhibited oxygen and glucose deprivation-induced [(3)H]glycine release. It is concluded that reduction of the N-methyl-d-aspartate receptor coagonist glycine concentrations in hypoxic conditions by glycine transporter type-1 inhibitors may decrease N-methyl-d-aspartate receptor-mediated neuronal toxicity and cell death in retinal tissue.