Evidence for the involvement of a carboxyl group in the vicinity of the MK801 and magnesium ion binding site of the N-methyl-D-aspartate receptor.

Chazot, P.L., Fotherby, A. and Stephenson, F.A. (1993) Evidence for the involvement of a carboxyl group in the vicinity of the MK801 and magnesium ion binding site of the N-methyl-D-aspartate receptor. Biochemical Pharmacology, 45 (3). pp. 605-610. 10.1016/0006-2952(93)90133-H.

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DOI: 10.1016/0006-2952(93)90133-H

Abstract

A series of protein modifying reagents were tested for their effects on the specific binding of [3H]MK801 to adult rat brain membranes. N-Bromosuccinimide, acetyl imidazole, 2,3-butanedione, 5,5'-dithiobis-(2-nitrobenzoic acid) and dithiothreitol all had no significant effect on binding. The carboxylic acid residue modification reagent, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC), inhibited [3H]MK801 specific binding in a dose-dependent manner with an IC50 = 1.9 mM. The inhibition by EDAC was due to a decrease in the Bmax with no change in KD. The inhibition of [3H]MK801 binding by EDAC was not prevented by prior incubation with competitive antagonists. Protection against EDAC inactivation was obtained, however, in a dose-dependent manner by preincubation with the divalent cations, Ca2+ and Mg2+, but not Zn2+. These results suggest that EDAC modifies an important carboxyl group located within the voltage-dependent Mg2+ binding site of the N-methyl-D-aspartate receptor. This modification yields a decrease in the specific [3H]MK801 binding activity thus demonstrating a close association between the two allosteric regulatory sites.

Item Type:Article
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2574
Journal or Publication Title:Biochemical Pharmacology
Deposited By:Library Staff
Deposited On:25 Nov 2011 15:45
Last Modified:25 Nov 2011 15:45

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