A rapid filtration assay for the glycine binding site on the NMDA receptor in rat cortical membranes using [3H]dichlorokynurenic acid

J Pharm Pharmacol. 1992 Oct;44(10):812-6. doi: 10.1111/j.2042-7158.1992.tb03211.x.

Abstract

A filtration binding assay using [3H]dichlorokynurenic acid to label the glycine binding site on the N-methyl-D-aspartic acid receptor has been evaluated on rat cortical membranes. This ligand binds to a single population of binding sites following mass action kinetics with a KD of 29 nM and a capacity of 5.73 pmol (mg protein)-1. The pharmacological specificity of the binding site is identical to that previously reported for this binding site using [3H]glycine as a radioligand. Agonists showed lower affinity and antagonists higher affinity when [3H]dichlorokynurenic acid was used compared with [3H]glycine. The higher affinity of [3H]dichlorokynurenic acid compared with [3H]glycine make it the more suitable compound with which to label the glycine site.

MeSH terms

  • Animals
  • Binding Sites
  • Cerebral Cortex / metabolism*
  • Filtration
  • Glycine / metabolism*
  • In Vitro Techniques
  • Kynurenic Acid / analogs & derivatives*
  • Male
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Tritium

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Tritium
  • Kynurenic Acid
  • 5,7-dichlorokynurenic acid
  • Glycine