title: Temporal alteration of spreading depression by the glycine transporter type-1 inhibitors NFPS and Org-24461 in chicken retina.
abstract: 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.
authors.affiliation: Division of Preclinical Research, EGIS Pharmaceuticals Plc, Bokenyfoldi ut 116, 1165 Budapest, Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Kertesz
authors.forename: Geza
authors.initials: G
authors.lastname: Szabo
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Udvari
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Levay
authors.forename: Peter
authors.initials: P
authors.lastname: Matyus
authors.forename: Laszlo G
authors.initials: LG
authors.lastname: Harsing
mesh_terms: D000818:Animals; D016466:CHO Cells; D002645:Chickens; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D050487:Glycine Plasma Membrane Transport Proteins; C435025:N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-3-(4'-phenylphenoxy)propyl)sarcosine; C479537:Org 24461; D016202:N-Methylaspartate; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D012521:Sarcosine