Publication details for Dr P ChazotChazot, PL., Lawrence, S. & Thompson, CL. (2002). Studies on the subtype selectivity of CP-101,606: evidence for two classes of NR2B-selective NMDA receptor antagonists. Neuropharmacology 42(3): 319-324.
- Publication type: Journal papers: academic
- ISSN/ISBN: 0028-3908
- DOI: 10.1016/S0028-3908(01)00191-5
- Keywords: NR1/NR2A/NR2B; NMDA receptor; Racemic [3H]CP-101,606; Immunoaffinity chromatography; Subtype-selectivity
- View online: Online version
- Durham research online: DRO record
Author(s) from Durham
The subtype-selectivity of racemic [3H]CP-101,606, a novel high-affinity NMDA receptor radioligand was determined using defined recombinant NMDA receptor subunits expressed in HEK 293 cells. [3H]CP-101,606 binds to adult rodent forebrain and NR1/NR2B receptors expressed in HEK 293 cells with KD=4.2 nM and 6.0 nM, respectively. In contrast, no high affinity specific binding was detected to NR1, NR2A, NR2B subunits expressed alone or NR1/NR2A receptors. HEK 293 cells were transfected with NR1, NR2A and NR2B receptor subunits and complexes comprising all three subunits were isolated by anti-NR2A immunoaffinity chromatography. Based on immunoblotting with subunit-selective antibodies, the immunopurified material contained all three NMDA receptor subunit polypeptides. However, in contrast to parallel studies in which high affinity [3H]Ro-25,6981 binding activity was observed, no high affinity [3H]CP-101,606 binding sites were detected to the immunopurified material. This study provides further evidence for two distinct classes of NR2B-directed NMDA receptor antagonists, one which binds with high affinity irrespective whether another NR2 subunit type is present (Ro-25,6981) and a second class which is affected significantly by the presence of another NR2 subunit type within the receptor complex, exemplified by CP-101,606.