Temporal alteration of spreading depression by the glycine transporter type-1 inhibitors NFPS and Org-24461 in chicken retina.

Szabolcs Kertesz, Geza Szabo, Szabolcs Udvari, Gyorgy Levay, Peter Matyus, Laszlo G Harsing

Division of Preclinical Research, EGIS Pharmaceuticals Plc, Bokenyfoldi ut 116, 1165 Budapest, Hungary.

Brain research 2013 Jan 25

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We used isolated chicken retina to induce spreading depression by the glutamate receptor agonist N-methyl-d-aspartate. The N-methyl-d-aspartate-induced latency time of spreading depression was extended by the glycine(B) binding site competitive antagonist 7-chlorokynurenic acid. Addition of the glycine transporter type-1 inhibitors NFPS and Org-24461 reversed the inhibitory effect of 7-chlorokynurenic acid on N-methyl-d-aspartate-evoked spreading depression. The glycine uptake inhibitory activity of Org-24461, NFPS, and some newly synthesized analogs of NFPS was determined in CHO cells stably expressing human glycine transporter type-1b isoform. Compounds, which failed to inhibit glycine transporter type-1, also did not have effect on retinal spreading depression. These experiments indicate that the spreading depression model in chicken retina is a useful in vitro test to determine activity of glycine transporter type-1 inhibitors. In addition, our data serve further evidence for the role of glycine transporter type-1 in retinal neurotransmission and light processing. Copyright © 2012 Elsevier B.V. All rights reserved.

Citation

Szabolcs Kertesz, Geza Szabo, Szabolcs Udvari, Gyorgy Levay, Peter Matyus, Laszlo G Harsing. Temporal alteration of spreading depression by the glycine transporter type-1 inhibitors NFPS and Org-24461 in chicken retina. Brain research. 2013 Jan 25;1492:1-6