A Glycine Site Associated with N-Methyl-d-Aspartic Acid Receptors: Characterization and Identification of a New Class of Antagonists
Version of Record online: 5 OCT 2006
Journal of Neurochemistry
Volume 52, Issue 4, pages 1319–1328, April 1989
How to Cite
Kessler, M., Terramani, T., Lynch, G. and Baudry, M. (1989), A Glycine Site Associated with N-Methyl-d-Aspartic Acid Receptors: Characterization and Identification of a New Class of Antagonists. Journal of Neurochemistry, 52: 1319–1328. doi: 10.1111/j.1471-4159.1989.tb01881.x
- Issue online: 5 OCT 2006
- Version of Record online: 5 OCT 2006
- Received July 6, 1988; revised manuscript received September 30, 1988; accepted October 7, 1988.
- N-Methyl-d-aspartic acid receptor;
- Kynurenic acid
Abstract Membranes from rat telencephalon contain a single class of strychnine-insensitive glycine sites. That these sites are associated with N-methyl-d-aspartic acid (NMDA) receptors is indicated by the observations that [3H]glycine binding is selectively modulated by NMDA receptor ligands and, conversely, that several amino acids interacting with the glycine sites increase [3H]N-[1-(2-thienyl)cyclohexyl]piper-idine ([3H]TCP) binding to the phencyclidine site of the NMDA receptor. The endogenous compound kynurenate and several related quinoline and quinoxaline derivatives inhibit glycine binding with affinities that are much higher than their affinities for glutamate binding sites. In contrast to glycine, kynurenate-type compounds inhibit [3H]TCP binding and thus are suggested to form a novel class of antagonists of the NMDA receptor acting through the glycine site. These results suggest the existence of a dual and opposite modulation of NMDA receptors by endogenous ligands.