Characterization of the non-competitive antagonist binding site of the NMDA receptor in dark Agouti rats

Wen Lin Sun, William D. Wessinger

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The ability of non-competitive NMDA antagonists and other selected compounds to inhibit [3H]MK-801 binding to the NMDA receptor in brain membranes was evaluated in female, dark Agouti rats. In homologous competition binding studies the average apparent affinity (KD) of [ 3H]MK-801 for its binding site was 5.5 nM and the binding site density (Bmax) was 1.83 pmol/mg protein. Inhibition of [ 3H]MK-801 binding by non-competitive NMDA antagonists was best described with a one-site competition model and the average Hill coefficients were -1. A series of eight non-competitive NMDA antagonists inhibited [ 3H]MK-801 binding with the following rank order of affinity (K i, nM): MK-801 (5.5) > dexoxadrol (21.5) ≥ TCP (24.2) > phencyclidine (100.8) > (+)-SKF 10,047 (357.7) > dextrorphan (405.2) > ketamine (922.2) > dextromethorphan (2913). These inhibition binding constants determined in dark Agouti rat brain membranes were significantly correlated (P = 0.0002; r2 = 0.95) with previously reported values determined in Sprague-Dawley rats [Wong et al., 1988, J. Neurochem. 50, 274-281]. Despite significant differences in metabolic capability between these strains, the central nervous system NMDA receptor ion channel shares similar characteristics.

Original languageEnglish (US)
Pages (from-to)1405-1415
Number of pages11
JournalLife Sciences
Volume75
Issue number12
DOIs
StatePublished - Aug 6 2004
Externally publishedYes

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Dizocilpine Maleate
N-Methyl-D-Aspartate Receptors
Rats
Binding Sites
N-Methylaspartate
Brain
Dextrorphan
Dextromethorphan
Membranes
Phencyclidine
Competitive Binding
Ketamine
Neurology
Ion Channels
Sprague Dawley Rats
Central Nervous System
Dasyproctidae
Proteins

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Characterization of the non-competitive antagonist binding site of the NMDA receptor in dark Agouti rats. / Sun, Wen Lin; Wessinger, William D.

In: Life Sciences, Vol. 75, No. 12, 06.08.2004, p. 1405-1415.

Research output: Contribution to journalArticle

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