Receptor to glutamate NMDA-type: The functional diversity of the NR1 isoforms and pharmacological properties

Current Pharmaceutical Design

Volumn 19, Issue 38, 2013, Pages 6709-6719

  Flores Soto, Mario Eduardo ^a   Chaparro Huerta, Verónica ^b   Escoto Delgadillo, Martha ^c,d   Ureña Guerrero, Mónica Elisa ^e   Camins, Antoni ^f   Beas Zarate, Carlos ^b,e  

^a Instituto de Neurociencias   (Mexico)

^b Lab Neurobiol Cel Y Molec   (Mexico)

^c CENTRO DE INVESTIGACIÓN BIOMÉDICA DE OCCIDENTE   (Mexico)

^d UNIVERSITY OF GUADALAJARA   (Mexico)

^e CUCBA   (Mexico)

^f UNIVERSITY OF BARCELONA   (Spain)

Author keywords

Excitotoxicity; Isoform; NMDA receptor; NR1 Subunit; NR2 Subunit

Indexed keywords

DIMER; GLUTAMATE RECEPTOR; IONOTROPIC RECEPTOR; ISOPROTEIN; MESSENGER RNA; METABOTROPIC RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 1; PROTEIN VARIANT; NR1 NMDA RECEPTOR; NR2A NMDA RECEPTOR; NR2B NMDA RECEPTOR; NR3A NMDA RECEPTOR;

ALZHEIMER DISEASE; ARTICLE; ELECTROPHYSIOLOGY; EXCITOTOXICITY; HUNTINGTON CHOREA; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; PROTEIN SUBUNIT; RECEPTOR AFFINITY; ANIMAL; CHEMISTRY; DRUG EFFECT; HUMAN; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY;

ALZHEIMER DISEASE; ANIMALS; HUMANS; HUNTINGTON DISEASE; PROTEIN ISOFORMS; RECEPTORS, N-METHYL-D-ASPARTATE;

EID: 84906289352     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612811319380003     Document Type: Article

References (89)

1. [1] Orrego F, Villanueva S. The chemical nature of the main central excitatory transmitter: a critical appraisal based upon release stud ies and synaptic vesicle localization. Neuroscience 1993; 56(3): 539-55.
2. [2] Dingledine R, McBain CJ. Glutamate and Aspartate. In: Siegel GJ, Albers RW, Brady S, Price DL. Basic Neurochemistry, Seventh Edition: Molecular, Cellular and Medical Aspects. (Eds), Academic Press. 2005
3. [3] Südhof TC. Intracellular trafficking. In Siegel GJ, Albers RW, Brady S, Price DL. Basic Neurochemistry, Seventh Edition: Molecular, Cellular and Medical Aspects. Eds, Academic Press. 2005.
4. [4] Rodríguez A, López Colomé AM. Características farmacológicas de las subunidades de los receptores de glutamato del tipo N-metil-D-aspartato (NMDA). Salud Ment 1997; 20(4): 39-47
5. [5] Ozawa S, Kamiya H, Tsuzuki K. Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 1998; 54(5): 581-618.
6. [6] Michaelis EK. Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog Neurobiol 1998; 54(4): 369-415.
7. [7] Llansola M, Sanchez-Perez A, Cauli O, Felipo V. Modulation of NMDA receptors in the cerebellum. Properties of the NMDA receptor that modulate its function. Cerebellum 2005; 4(3): 134-61.
8. [8] Lynch DR, Guttmann RP. NMDA receptor pharmacology: perspectives from molecular biology. Curr Drug Targets 2001; 2(3): 215-31.
9. [9] Schorge S, Colquhoun D. Studies of NMDA receptor function and stoichiometry with truncated and tándem subunits. J Neurosci 2003; 23(4): 1151-8.
10. [10] Papadakis M, Hawkins LM, Stephenson FA. Appropriate NR1-NR1 disulfide-linked homodimer formation is requisite for efficient expression of functional, cell surface N-methyl-D-aspartate NR1/NR2 receptors. J Biol Chem 2004; 279(15): 14703-12.
11. [11] Schüler T, Mesic I, Madry C, Bartholomäus I, Laube B. Formation of NR1/NR2 and NR1/NR3 heterodimers constitutes the initial step in N-methyl-D-aspartate receptor assembly. J Biol Chem 2008; 283(1): 37-46.
12. [12] Das S, Sasaki YF, Rothe T, et al. Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature 1998; 393(6683): 377-81
13. [13] Chatterton JE, Awobuluyi M, Premkumar LS, et al. Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 2002; 415(6873): 793-8
14. [14] Laurie DJ, Seeburg PH. Regional and developmental heterogeneity in splicing of the rat brain NMDAR1 mRNA. J Neurosci 1994; 14: 3180-94.
15. [15] Zukin RS., Bennett MV. Alternatively spliced isoforms of the NMDARI receptor subunit. Trends Neurosci 1995; 18(7): 306-13.
16. [16] Holmes KD, Mattar PA, Marsh DR, Weaver LC, Dekaban GA. The N-methyl-D-aspartate receptor splice variant NR1-4 C-terminal domain. Deletion analysis and role in subcellular distribution. J Biol Chem 2002; 277(2): 1457-68.
17. [17] Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev 1999; 51(1): 7-61.
18. [18] Traynelis SF, Hartley M, Heinemann SF. Control of proton sensitivity of the NMDA receptor by RNA splicing and polyamines. Science 1995; 268(5212): 873-6.
19. [19] Lyuboslavsky P, French A, Le P, et al. Molecular determinants of proton-sensitive N-methyl-D-aspartate receptor gating. Low CM, Mol Pharmacol 2003; 63(6): 1212-22.
20. [20] Tingley WG, Roche KW, Thompson AK, Huganir RL. Regulation of NMDA receptor phosphorylation by alternative splicing of the C-terminal domain. Nature 1993; 364(6432): 70-3.
21. [21] Bradley J, Carter SR, Rao VR, Wang J, Finkbeiner S. Splice variants of the NR1 subunit differentially induce NMDA receptor-dependent gene expression. J Neurosci 2006; 26(4): 1065-76.
22. [22] Ehlers MD, Zhang S, Bernhadt JP, Huganir RL. Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit. Cell 1996; 84(5): 745-55.
23. [23] Rycroft BK, Gibb AJ. Inhibitory interactions of calcineurin (phos-phatase 2B) and calmodulin on rat hippocampal NMDA receptors. Neuropharmacology 2004; 47(4): 505-14.
24. [24] Okabe S, Miwa A, Okado H. Alternative splicing of the C-terminal domain regulates cell surface expression of the NMDA receptor NR1 subunit. J Neurosci 1999; 19(18): 7781-92.
25. [25] Scott DB, Blanpied TA, Swanson GT, Zhang C, Ehlers MD. An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing. J Neurosci 2001; 21(9): 3063-72.
26. [26] Styley S, Roche KW, McCallum J, Sans N, Wenthold RJ. PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants. Neuron 2000; 28(3): 887-98.
27. 27[] Kreutz MR, Böckers TM, Bockmann J, et al. Axonal injury alters alternative splicing of the retinal NR1 receptor: the preferential expression of the NR1b isoforms is crucial for retinal ganglion cell survival. J Neurosci 1998; 18(20): 8278-91.
28. [28] Virgo L, Dekkers J, Mentis GZ, Navarrete R, de Belleroche J. Changes in expression of NMDA receptor subunits in the rat lumbar spinal cord following neonatal nerve injury. Neuropathol Appl Neurobiol 2000; 26(3): 258-72.
29. [29] Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. Developmental and regional expression in the rat brain y functional properties of four NMDA receptors. Neuron 1994; 12: 529-40.
30. [30] Vicini S, Wang JF, Li JH, et al. Functional and pharmacological differences between recombinant N-methyl-D-aspartate receptors. J Neurophysiol 1998; 79(2): 555-66.
31. [31] Erreger K, Dravid SM, Banke TG, Wyllie DJ, Traynelis SF. Subunit-specific gating controls rat NR1/NR2A and NR1/NR2B NMDA channel kinetics and synaptic signalling profiles. J Physiol 2005; 563(Pt 2): 345-58.
32. [32] Lester RA, Clements JD, Westbrook GL, Jahr CE. Channel kinetics determine the time course of NMDA receptor mediated synaptic currents. Nature 1990; 346(6284): 565-7.
33. [33] Sprengel R, Suchanek B, Amico C, et al. Importance of the intra-cellular domain of NR2 subunits for NMDA receptor function in vivo. Cell 1998; 92(2): 279-89.
34. [34] Hawkins LM, Prybylowski K, Chang K, Moussan C, Stephenson FA, Wenthold RJ. Export from the endoplasmic reticulum of assembled N-methyl-D-aspartic acid receptors is controlled by a motif in the c terminus of the NR2 subunit. J Biol Chem 2004; 279(28): 28903-10.
35. [35] Kornau HC, Schenker LT, Kennedy MB, Seeburg PH. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 1995; 269(5231): 1737-40.
36. [36] Chung HJ, Huang YH, Lau LF, Huganir RL. Regulation of the NMDA receptor complex and trafficking by activity-dependent phosphorylation of the NR2B subunit PDZ ligand. J Neurosci 2004; 24(45): 10248-59.
37. [37] Leonard AS, Hell JW. Cyclic AMP-dependent protein kinase y protein kinase C phosphorylate N-methyl-D-aspartate receptors at different sites. J Biol Chem 1997; 272(18): 12107-15.
38. [38] Scott DB, Blanpied TA, Ehlers MD. Coordinated PKA and PKC phosphorylation suppresses RXR-mediated ER retention and regulates the surface delivery of NMDA receptors. Neuropharmacology 2003; 45(6): 755-67.
39. [39] Lau G.C, Saha S, Faris R, Russek S. J. Up-regulation of NMDAR1 subunit gene expression in cortical neurons via a PKA-dependent pathway. J Neurochem 2004; 88(3): 564-75.
40. [40] Sala C, Sheng M. The fyn art of N-methyl-D-aspartate receptor phosphorylation. Proc Natl Acad Sci USA 1999; 96(2): 335-7.
41. 41[] Chian-Ming LOW, Karen Siaw-Ling WEE. New Insights into the Not-So-New NR3 Subunits of N-Methyl- D-aspartate Receptor: Localization, Structure, and Function. Mol Pharmacol 2010; 78: 1-11.
42. [42] Chatterton JE, Awobuluyi M, Premkumar LS, et al. Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 2002; 415(6873): 793-8.
43. [43] Cavara, N.A., Orth, A., and Hollmann, M 2009. Effects of NR1 splicing on NR1/NR3B-type excitatory glycine Receptors. BMC Neuroscience 2009; 10(32): 1-11.
44. [44] Cull-Candy S, Brickley S, Farrant M. NMDA receptor subunits: diversity, development and disease. Curr Opin Neurobiol 2001; 11(3): 327-35.
45. [45] Burnashev N, Zhou S, Neher E, Sakmann B. Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and Kainate receptor subtypes. J Physiol 1995; 485(2): 403-18.
46. [46] Jatzke C, Watanabe J, Wollmuth LP. Voltage and concentration dependence of Ca(2+) permeability in recombinant glutamate receptor subtypes. J Physiol 2002; 538 (Pt 1): 25-39.
47. [47] Morrisett R. Electrophysiologic characteristics of heteromeric recombinant NMDA receptors: Comparison with native receptors. En: The lonotropic Glutamate Receptors. Monaghan DT, Wen-thold RJ (Eds) Humana Press, Nueva Jersey 1997.
48. [48] Buller AL, Larson HC, Schneider BE, Beaton JA, Morrisett RA, Monaghan DT. The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition. J Neurosci 1994; 14(9): 5471-84.
49. [49] Erreger K, Geballe MT, Kristensen A, et al. Subunit-specific agonist activity at NR2A-, NR2B-, NR2C-, and NR2D-containing N-methyl-D-aspartate glutamate receptors. Mol Pharmacol 2007; 72(4): 907-20.
50. [50] Watanabe M, Inoue Y, Sakimura K, Mishina M. Developmental changes in distribution of NMDA receptor channel subunit mRNAs. Neuroreport 1992; 3: 1138-40.
51. [51] Goebel DJ, Poosch MS. NMDA receptor subunit gene expression in the rat brain: a quantitative analysis of endogenous mRNA levels of NR1Com, NR2A, NR2B, NR2C, NR2D and NR3A. Brain Res Mol Brain Res 1999; 69(2): 164-70.
52. [52] Kurkó D, Dezso P, Boros A, Kolok S, Fodor L, Nagy J, Szom-bathelyi Z. Inducible expression and pharmacological characterization of recombinant rat NR1a/NR2A NMDA receptors. Neurochem Int 2005; 46(5): 369-79.
53. [53] Lu C, Fu Z, Karavanov I, Yasuda RP, Wolfe BB, Buonanno A, Vicini S. NMDA receptor subtypes at autaptic synapses of cerebel-lar granule neurons. J Neurophysiol 2006; 96(5): 2282-94.
54. [54] Cathala L, Misra C, Cull-Candy S. Developmental profile of the changing properties of NMDA receptors at cerebellar mossy fiber-granule cell synapses. J Neurosci 2000; 20(16): 5899-905.
55. [55] Wenzel A, Benke D, Mohler H, Fritschy JM. N-methyl-D-aspartate receptors containing the NR2D subunit in the retina are selectively expressed in rod bipolar cells. Neuroscience 1997; 78 (4): 1105-12.
56. [56] Olney JW. New insights and new issues in developmental neuro-toxicology. Neurotoxicology 2002; 23(6): 659-68.
57. [57] Lapouble E, Montécot C, Sevestre A, Pichon J. Phosphinothricin induces epileptic activity via nitric oxide production through NMDA receptor activation in adult mice. Brain Res 2002; 957(1): 46-52.
58. [58] Nishizawa Y. Glutamate release and neuronal damage in ischemia. Life Sci 2001; 69(4): 369-81.
59. 59[] Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 2000; 1(2): 120-9.
60. [60] Martin LJ, Al-Abdulla NA, Brambrink AM, Kirsch JR, Sieber FE, Portera-Cailliau C. Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: A perspective on the contributions of apoptosis and necrosis. Brain Res Bull 1998; 46(4): 281-309.
61. [61] Mattson MP, LaFerla FM, Chan SL, Leissring MA, Shepel PN, Geiger JD. Calcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders. Trends Neurosci 2000; 23(5): 222-9.
62. [62] Mattson MP, Culmsee C, Yu ZF. Apoptotic and antiapoptotic mechanisms in stroke. Cell Tissue Res 2000; 301(1): 173-87.
63. [63] Kawasaki H, Morooka T, Shimohama S, et al. Activation and involvement of p38 mitogen-activated protein kinase in glutamate-induced apoptosis in rat cerebellar granule cells. J Biol Chem 1997; 272(30): 18518-21.
64. [64] Olney JW. Excitotoxicity, apoptosis and neuropsychiatric disorders. Curr Opin Pharmacol., 2003, 3(1): 101-109.
65. [65] Antonelli T, Fuxe K, Tomasini MC, et al. Neurotensin receptor mechanisms and its modulation of glutamate transmission in the brain: relevance for neurodegenerative diseases and their treatment. Prog Neurobiol 2007; 83(2): 92-109.
66. [66] Gardoni F, Di Luca M. New targets for pharmacological intervention in the glutamatergic synapse. Eur J Pharmacol 2006, 545(1): 2-10.
67. [67] Zou X, Patterson TA, Sadovova N, et al. Potential neurotoxicity of ketamine in the developing rat brain. Toxicol Sci., 2009, 108(1): 149-58.
68. [68] Rammes G, Danysz W, Parsons CG. Pharmacodynamics of me-mantine: an update. Curr Neuropharmacol., 2008, 6(1): 55-78.
69. [69] Wu LJ, Zhuo M. Targeting the NMDA receptor subunit NR2B for the treatment of neuropathic pain. Neurotherapeutics 2009, 6(4): 693-702.
70. [70] Khosravani H, Zhang Y, Tsutsui S, et al. Prion protein attenuates excitotoxicity by inhibiting NMDA receptors 2008. J Cell Biol 181(3): 551-65.
71. [71] Duncan GE, Inada K, Farrington JS, Koller BH. Seizure responses and induction of Fos by the NMDA agonist (tetrazol-5-yl)glycine in a genetic model of NMDA receptor hypofunction. Brain Res 2008; 1221: 41-8.
72. [72] Cui B, Wu M, She X. Effects of chronic noise exposure on spatial learning and memory of rats in relation to neurotransmitters and NMDAR2B alteration in the hippocampus. J Occup Health 2009; 51(2): 152-8.
73. [73] Kim YS, Chang HK, Lee JW, et al. Protective effect of gabapentin on N-methyl-D-aspartate-induced excitotoxicity in rat hippocampal CA1 neurons. J Pharmacol Sci 2009; 109(1): 144-7.
74. [74] Liu YH, Wang L, Wei LC, Huang YG, Chen LW. Up-regulation of D-serine might induce GABAergic neuronal degeneration in the cerebral cortex and hippocampus in the mouse pilocarpine model of epilepsy. Neurochem Res 2009; 34(7): 1209-18.
75. [75] Toscano CD, Kingsley PJ, Marnett LJ, Bosetti F. NMDA-induced seizure intensity is enhanced in COX-2 deficient mice. Neurotoxi-cology 2008; 29(6): 1114-20.
76. [76] Olney JW, Wozniak DF, Farber NB. Excitotoxic neurodegenera-tion in Alzheimer's disease. New hypothesis and new therapeutic strategies. Arch Neurol 1997; 54: 1234-40.
77. [77] Coleman PD, Yao PJ. Synaptic slaughter in Alzheimer's disease. Neurobiol Aging 2003; 24: 1023-7.
78. [78] Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci 2007; 27: 2866-75.
79. [79] Snyder EM, Nong Y, Almeida CG, et al. Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 2005; 8: 1051-8.
80. [80] Coyle JT, Schwarcz R. Lesion of striatal neurones with kainic acid provides a model for huntington chorea. Nature 1976; 263: 244-6.
81. [81] Petersen A, Mani K, Brundin P. Recent advances on the patho-genesis Huntington disease. Exp Neurol 1999; 157: 1-18.
82. [82] Zeron MM, Hansson O, Chen N, et al. Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington‘s disease. Neuron 2002; 33: 849-60.
83. [83] Landwehrmeyer GB, Standaert DG, Testa CM, Penney JB, Young AB. NMDA receptor subunit mRNA expression by projection neurons and interneurons in rat striatum. J Neurosci 1995; 15: 5297-307.
84. [84] Standaert DG, Landwehrmeyer GB, Kerner JA, Penney JB, Young AB. Expression of NMDAR2D glutamate receptor subunit mRNA in neurochemically identified interneurons in the rat neostriatum, neocortex and hippocampus. Brain Res Mol Brain Res 1996; 42: 89-102.
85. [85] Zeron MM, Fernandes HB, Krebs C, et al. Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington‘s disease. Mol Cell Neurosci 2004; 25: 469-79.
86. [86] Li L, Murphy TH, Hayden MR, Raymond LA. Enhanced striatal NR2B-containing N-methyl-D-aspartate receptor-mediated synap-tic currents in a mouse model of Huntington disease. J Neuro-physiol 2004; 92: 2738-46.
87. [87] Li L, Fan M, Icton CD, et al. Role of NR2B-type NMDA receptors in selective neurodegeneration in Huntington disease. Neurobiol Aging 2003; 24: 1113-21.
88. [88] Standaert DG, Friberg IK, Landwehrmeyer GB, Young AB, Penney JB. Expression of NMDA glutamate receptor subunit mRNAs in neurochemically identified projection and interneurons in the striatum of the rat. Brain Res Mol Brain Res 1999; 64: 11-23.
89. [89] Rivera-Cervantes MC, Flores-Soto ME, Chaparro-Huerta V, et al. Changes in hippocampal NMDA-R subunit composition induced by exposure of neonatal rats to L-glutamate. Int J Dev Neurosci 2009; 27(2): 197-204.