N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. The NMDA receptor channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heterotetramers composed of two molecules of the key receptor subunit NMDAR1 (GRIN1) and two drawn from one or more of the four NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D). The NR2 subunit acts as the agonist binding site for glutamate, one of the predominant excitatory neurotransmitter receptors in the mammalian brain.
NR2B has been associated with age- and visual-experience-dependent plasticity in the neocortex of rats, where an increased NR2B/NR2A ratio correlates directly with the stronger excitatory LTP in young animals. This is thought to contribute to experience-dependent refinement of developing cortical circuits.
Both mice and rats that were engineered to over-express GRIN2B in their brains have increased mental ability.
Evt 101, a selective NR2B receptor antagonist. This compound was tested as a potentially fast-acting antidepressant. In 2011 it was voluntarily withdrawn from a Phase II clinical study in treatment-resistant depression due to an unsatisfactory toxicity profile.
^Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M (January 1997). "Competitive binding of alpha-actinin and calmodulin to the NMDA receptor". Nature. 385 (6615): 439–42. doi:10.1038/385439a0. PMID9009191.
^ abcInanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y (June 2002). "Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses". American Journal of Physiology. Cell Physiology. 282 (6): C1396–403. doi:10.1152/ajpcell.00615.2001. PMID11997254.
^ abcSans N, Prybylowski K, Petralia RS, Chang K, Wang YX, Racca C, Vicini S, Wenthold RJ (June 2003). "NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex". Nature Cell Biology. 5 (6): 520–30. doi:10.1038/ncb990. PMID12738960.
^ abLim IA, Hall DD, Hell JW (June 2002). "Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102". The Journal of Biological Chemistry. 277 (24): 21697–711. doi:10.1074/jbc.M112339200. PMID11937501.
^Niethammer M, Valtschanoff JG, Kapoor TM, Allison DW, Weinberg RJ, Craig AM, Sheng M (April 1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90". Neuron. 20 (4): 693–707. doi:10.1016/s0896-6273(00)81009-0. PMID9581762.
^Jo K, Derin R, Li M, Bredt DS (June 1999). "Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex". The Journal of Neuroscience. 19 (11): 4189–99. doi:10.1523/JNEUROSCI.19-11-04189.1999. PMID10341223.
Schröder HC, Perovic S, Kavsan V, Ushijima H, Müller WE (1998). "Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death". Neurotoxicology. 19 (4–5): 683–8. PMID9745929.
Nagy J (June 2004). "The NR2B subtype of NMDA receptor: a potential target for the treatment of alcohol dependence". Current Drug Targets. CNS and Neurological Disorders. 3 (3): 169–79. doi:10.2174/1568007043337409. PMID15180478.
Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (September 1995). "Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95". Science. 269 (5231): 1737–40. doi:10.1126/science.7569905. PMID7569905.
Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (March 1995). "Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity". Annals of Neurology. 37 (3): 373–80. doi:10.1002/ana.410370314. PMID7695237.
Mandich P, Schito AM, Bellone E, Antonacci R, Finelli P, Rocchi M, Ajmar F (July 1994). "Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12". Genomics. 22 (1): 216–8. doi:10.1006/geno.1994.1366. PMID7959773.
Adams SL, Foldes RL, Kamboj RK (January 1995). "Human N-methyl-D-aspartate receptor modulatory subunit hNR3: cloning and sequencing of the cDNA and primary structure of the protein". Biochimica et Biophysica Acta. 1260 (1): 105–8. doi:10.1016/0167-4781(94)00189-a. PMID7999784.
Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY (March 1994). "Changing subunit composition of heteromeric NMDA receptors during development of rat cortex". Nature. 368 (6467): 144–7. doi:10.1038/368144a0. PMID8139656.
Roche KW, Raymond LA, Blackstone C, Huganir RL (April 1994). "Transmembrane topology of the glutamate receptor subunit GluR6". The Journal of Biological Chemistry. 269 (16): 11679–82. PMID8163463.
Lannuzel A, Lledo PM, Lamghitnia HO, Vincent JD, Tardieu M (November 1995). "HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i increase, alter [Ca2+]i homeostasis and induce neurotoxicity in human embryonic neurons". The European Journal of Neuroscience. 7 (11): 2285–93. doi:10.1111/j.1460-9568.1995.tb00649.x. PMID8563977.
Corasaniti MT, Melino G, Navarra M, Garaci E, Finazzi-Agrò A, Nisticò G (September 1995). "Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is prevented by NMDA receptor antagonists and inhibitors of nitric oxide and cyclooxygenase". Neurodegeneration. 4 (3): 315–21. doi:10.1016/1055-8330(95)90021-7. PMID8581564.
Niethammer M, Kim E, Sheng M (April 1996). "Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases". The Journal of Neuroscience. 16 (7): 2157–63. doi:10.1523/JNEUROSCI.16-07-02157.1996. PMID8601796.
Pittaluga A, Pattarini R, Severi P, Raiteri M (May 1996). "Human brain N-methyl-D-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120". AIDS. 10 (5): 463–8. doi:10.1097/00002030-199605000-00003. PMID8724036.
Hess SD, Daggett LP, Crona J, Deal C, Lu CC, Urrutia A, Chavez-Noriega L, Ellis SB, Johnson EC, Veliçelebi G (August 1996). "Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors". The Journal of Pharmacology and Experimental Therapeutics. 278 (2): 808–16. PMID8768735.
Müller BM, Kistner U, Kindler S, Chung WJ, Kuhlendahl S, Fenster SD, Lau LF, Veh RW, Huganir RL, Gundelfinger ED, Garner CC (August 1996). "SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo". Neuron. 17 (2): 255–65. doi:10.1016/S0896-6273(00)80157-9. PMID8780649.
Toggas SM, Masliah E, Mucke L (January 1996). "Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine". Brain Research. 706 (2): 303–7. doi:10.1016/0006-8993(95)01197-8. PMID8822372.
Dreyer EB, Lipton SA (December 1995). "The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid". The European Journal of Neuroscience. 7 (12): 2502–7. doi:10.1111/j.1460-9568.1995.tb01048.x. PMID8845955.