[3H]MDL 105,519 binds with equal high affinity to both assembled and unassembled NR1 subunits of the NMDA receptor.

Chazot, P.L., Reiss, C., Chopra, B. and Stephenson, F.A. (1998) [3H]MDL 105,519 binds with equal high affinity to both assembled and unassembled NR1 subunits of the NMDA receptor. European Journal of Pharmacology, 353 (1). pp. 137-140. 10.1016/S0014-2999(98)00431-2.

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DOI: 10.1016/S0014-2999(98)00431-2

Abstract

[3H]MDL 105,519 (((E)-3-(2-phenyl-2-carboxyethenyl)-4,6-dichloro-1[3H]-indole-2-ca rboxylic acid) is a novel radioligand which binds with high affinity, Kd = 2.5 nM, to the glycine site of adult rodent forebrain, N-methyl-D-aspartate subtype of glutamate receptors. As with other glycine site antagonists, the major determinants for high-affinity binding of [3H]MDL 105,519 resides upon the NRI subunit, and not the NR2 subunits. [3H]MDL 105,519 binds with equal affinity, Kd = 3 nM, to both NR1-1a or NR1-4b splice variants, as well as the NRI-1a/NR2A receptor expressed in human embryonic kidney (HEK) 293 cells. One percent Triton X-100/1 M NaCl solubilises with a recovery of 15+/-3%, a mixed pool of assembled and unassembled forebrain NR1 subunit polypeptides. In this preparation, the recovery of [3H]MK801 ((+)-5-[3H]methyl-10,11-dihydrodibenzo[alpha,d]cyclohepten-5 ,10-imine binding activity (7+/-1%) reflects the amount of assembled NR1 subunits whereas [3H]MDL 105,519 binds quantitatively, with a recovery of 19+/-4% and Kd = 3 nM, to both assembled and unassembled NRI subunits. Therefore, [3H]MDL 105,519 should prove a useful ligand, in conjunction with immunopurification approaches, to address the question of NMDA receptor subunit stoichiometry.

Item Type:Article
Uncontrolled Keywords:NMDA receptor; Glutamate receptor; Glycine; Triton X-100; NR1
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2553
Journal or Publication Title:European Journal of Pharmacology
Deposited By:Library Staff
Deposited On:25 Nov 2011 12:31
Last Modified:25 Nov 2011 12:31

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