title: [3H] 5,7-dichlorokynurenic acid, a high affinity ligand for the NMDA receptor glycine regulatory site.
abstract: The NMDA subtype of glutamate receptors is allosterically linked to a strychnine-insensitive glycine regulatory site. Kynurenic acid and its halogenated derivatives are non-competitive NMDA antagonists acting at the glycine site. We have prepared [3H] 5,7-dichlorokyrurenic acid (DCKA) as an antagonist radioligand and have characterized its binding. 3-Bromo-5,7-DCKA was catalytically dehalogenated in the presence of tritium gas and HPLC purified to yield [3H] 5,7-DCKA with a specific activity of 17.6 Ci/mmol. [3H] 5,7-DCKA bound to rat brain synaptosomes with a Kd of 69 +/- 23 nM and Bmax = 14.5 +/- 3.2 pmoles/mg protein. Binding was 65-70% specific at 10 nM [3H] 5,7-DCKA. This ligand is thus more selective and has higher affinity than [3H] glycine, in addition to being an antagonist.
authors.affiliation: DuPont/NEN Products, Boston, MA 02118.
authors.forename: S D
authors.initials: SD
authors.lastname: Hurt
authors.forename: B M
authors.initials: BM
authors.lastname: Baron
mesh_terms: D000818:Animals; D005998:Glycine / Q000378:metabolism*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D008024:Ligands; D015394:Molecular Structure; D011869:Radioligand Assay; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014316:Tritium
chemical_list: D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid; D005998:Glycine