Studies on the subtype selectivity of CP-101,606: evidence for two classes of NR2B-selective NMDA receptor antagonists

Chazot, PL.; Lawrence, S.; Thompson, CL.

Abstract

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.

Citation

Chazot, P., Lawrence, S., & Thompson, C. (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. https://doi.org/10.1016/s0028-3908%2801%2900191-5

• Journal Article Type: Article
• Publication Date: Mar 1, 2002
• Deposit Date: May 18, 2007
• Journal: Neuropharmacology
• Print ISSN: 0028-3908
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 42
• Issue: 3
• Pages: 319-324
• DOI: https://doi.org/10.1016/s0028-3908%2801%2900191-5
• Keywords: NR1/NR2A/NR2B, NMDA receptor, Racemic [3H]CP-101,606, Immunoaffinity chromatography, Subtype-selectivity.
• Public URL: https://durham-repository.worktribe.com/output/1589873