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T. Zarnowski, M. Bialek, R. Rejdak, T. Kocki, Z. Zagorski, W.A. Turski; Influence of Excitatory Amino Acids upon Kynurenic Acid Synthesis in Bovine Retinal Slices . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2924.
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Purpose: Kynurenic acid (KYNA), the tryptophan metabolite, endogenous NMDA antagonist is a putative endogenous neuroprotectant synthesized in the eye along the kynurenine pathway. The purpose of the present study was to investigate the effect of excitatory amino acids upon KYNA production in bovine retinal slices. Methods: Adult bovine retinas were chopped in slices and placed at culture wells. De novo KYNA production was investigated according to the method of Turski et al. (1988). Quantitative analysis of newly synthesised KYNA was carried out using an HPLC system and detected fluorimetrically according to the method of Shibata. Glutamate, aspartate and kainate were tested. Results: Glutamate at the concentration of 1, 0,1, 0,01 and 0,001 mM reduced KYNA synthesis in the retinal slices to 23% (p<0,001), 35% (p<0,01), 70% (p<0,05) and 88% (NS), respectively. The concentration of glutamate reducing production of KYNA by 50% (IC50) was 0,035 mM (0,02-0,06). Aspartate at the concentration of 1, 0,1, 0,01 and 0,001 mM lowered KYNA synthesis in the retinal slices to 43% (p<0,001), 57% (p<0,001), 80% (p<0,01) and 95% (NS), respectively. The IC50 for aspartate was 0,32 mM (0,18 – 0,59). In contrast, kainic acid applied at the same concentrations turned out to be ineffective in diminishing KYNA synthesis. Conclusions: These data demonstrate the inhibiting effect of glutamate and aspartate on KYNA synthesis in bovine retinal slices.
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