The present address of Dr. P. M. Sweetnam is Pfizer, Central Research, Groton, CT 06340, U.S.A.
Interactions Between N-Acetylaspartylglutamate and AMPA, Kainate, and NMDA Binding Sites
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 63, Issue 5, pages 1714–1719, November 1994
How to Cite
Valivullah, H. M., Lancaster, J., Sweetnam, P. M. and Neale, J. H. (1994), Interactions Between N-Acetylaspartylglutamate and AMPA, Kainate, and NMDA Binding Sites. Journal of Neurochemistry, 63: 1714–1719. doi: 10.1046/j.1471-4159.1994.63051714.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Resubmitted manuscript received March 14, 1994; accepted March 21, 1994.
- Ionotropic glutamate receptors;
- NMDA receptors;
- Amino-3-hydroxy-5-methylisoxazole-4-propionic acid;
Abstract: The structure of N-acetylaspartylglutamate (NAAG) suggests this neuronal dipeptide as a candidate for interaction with discrete subclasses of ionotropic and metabotropic acidic amino acid receptors. A substantial difficulty in the assay of these interactions is posed by membrane-bound peptidase activity that converts the dipeptide to glutamate and N-acetylaspartate, molecules that will interfere with receptor assays. We have developed two sets of unique receptor assay conditions and applied one standard assay to measure the interactions, under equilibrium binding conditions, of [3H]kainate, [3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), and [3H]CGS-19755 with the three classes (kainate, quisqualate, and N-methyl-d-aspartate) of ionotropic glutamate receptors, while inhibiting peptidase activity against NAAG. Under these conditions, NAAG exhibits apparent inhibition constants (IC50) of 500, 790, and 8.8 µM in the kainate, AMPA, and CGS-19755 receptor binding assays, respectively. Glutamate was substantially more effective and less specific in these competition assays, with inhibition constants of 0.36, 1.1, and 0.37 µM. These data support the hypothesis that, relative to glutamate, NAAG functions as a specific, low potency agonist at N-methyl-d-aspartate subclass of ionotropic acidic amino acid receptors, but the peptide is not likely to activate directly the kainate or quisqualate subclasses of excitatory ionotropic receptors under physiologic conditions.