Novel Fourth Binding Sites of [3H]Spermidine within the NMDA Receptor Complex
N-Methyl-D-aspartic acid (NMDA)-sensitive subclass of the synaptic receptors for central excitatory amino acid neurotransmitters is supposed to form a receptor ion channel complex with modulatory glycine (Gly) binding sites which are insensitive to a classical Gly antagonist strychnine (for example, see review by Robinson and Coyle, 1987), based on the electrophysiological findings that Gly drastically potentiates in a strychnine-insensitive manner currents mediated by the NMDA-sensitive subclass without affecting those mediated by the other subclasses in cultured neuronal cells (Johnson and Ascher, 1987). The complex consists of at least three distinctly different sites; 1) NMDA recognition sites, 2) ion channel sites and 3) Gly recognition sites. The latter strychnine-insensitive Gly sites are referred to as GlyB sites to differentiate them from the strychnine-sensitive GlyA sites just for convenience’ sake (Ogita et al., 1989).
KeywordsSynaptic Membrane Excitatory Amino Acid Receptor NMDA Channel NMDA Receptor Complex Untreated Membrane
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- Davies, J., Evans, R.H., Herrling, P.L., Jones, A.W., Olverman, H.J., Pook, P., and Watkins, J.C., 1986, CPP, a new potent and selective NMDA antagonists. Depression of central neuron responses, affinity for D-[3H]AP5 binding sites on brain membranes and anticonvulsant activity, Brain Res., 382: 169–173.PubMedCrossRefGoogle Scholar
- Davies, S.N., Martin, D., Millar, J.D., Aram, J.A., Church, J., and Lodge, D., 1988, Differences in results from in vivo and in vitro studies on the use-dependency of N-methylaspartate antagonism by MK-801 and other phencyclidine receptor ligands, Eur. J. Pharmacol., 145: 141–151.PubMedCrossRefGoogle Scholar
- Kemp, J.A., Foster, A.C., Leeson, P.D., Priestley, T., Tridgett, R., Iversen, L.L., and Woodruff, G.N., 1988, 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex, Proc. Natl. Acad. Sci. U.S.A., 85: 6547–6550.PubMedCrossRefGoogle Scholar
- Lehmann, J., Hutchinson, A.J., McPherson, S.E., Mondadori, C., Schmutz, M., Sinton, C.M., Tsai, C., Murphy, D.E., Steel, D.J., Williams, M., Cheney, D.L., and Wood, P.L., 1988, CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist, J. Pharmacol. Exp. Ther., 246: 65–75.PubMedGoogle Scholar
- Ogita, K., and Yoneda, Y., 1990a, Temperature-independent binding of [3H](±)-3-(2-carboxypiperazin-4-yl)propyl-l-phosphonic acid in brain synaptic membranes treated with Triton X-100, Brain Res., in press.Google Scholar
- Ogita, K., Nabeshima, T., and Yoneda, Y., 1990, [3H]Thienylcyclohexyl-piperidine binding activity in brain synaptic membranes treated with Triton X-100, J. Neurochem., in press.Google Scholar
- Yoneda, Y., and Ogita, K., 1989b, Possible role of polyamines as modulators of NMDA receptor complex, Bull. Jap. Neurochem. Soc., 28: 136–137. (in Japanese)Google Scholar
- Yoneda, Y., Ogita, K., and Suzuki, T., 1988, Multiple binding sites on the NMDA receptor/ion channel complex in brain synaptic membranes, in: “Neurotransmitters: Focus on Excitatory Amino Acids,“ I. Kanazawa, ed., pp. 47–65, Excerpta Medica, Tokyo.Google Scholar
- Yoneda, Y., Ogita, K., Kouda, T., and Ogawa, Y., 1990a, Radioligand labeling of N-methyl-D-aspartic acid (NMDA) receptors by [3H](±)-3-(2-carboxypiperazin-4-yl)propyl-l-phosphonic acid in brain synaptic membranes treated with Triton X-100, Biochem. Pharmacol., 39: 225–228.PubMedCrossRefGoogle Scholar
- Yoneda, Y., Ogita, K., and Suzuki, T., 1990b, Interaction of strychnine-insensitive glycine binding with MK-801 binding in brain synaptic membranes, J. Neurochem., in press.Google Scholar