Metabotropni glutamatni receptor 1

Metabotropni glutamatni receptor 1
	; PDB prikaz baziran na 1ewk.
Dostupne strukture
	3KS9
Identifikatori
Simboli	GRM1; GPRC1A; GRM1A; MGLUR1; MGLUR1A; mGlu1
Vanjski ID	OMIM: 604473 MGI: 1351338 HomoloGene: 649 IUPHAR: mGlu1 GeneCards: GRM1 Gene
Ontologija gena
Molekularna funkcija	• aktivnost prenosnika signala; • receptorska aktivnost; • aktivnost G-protein spregnutog receptora; • aktivnost glutamatnog receptora; • vezivanje estrogenskog receptora;
Celularna komponenta	• nukleus; • mikrozom; • ćelijska membrana; • integralno sa ćelijskom membranom; • postsinaptička gustina; • akson; • presinaptička membrana; • dendritna osnova;
Biološki proces	• aktivacija MAPKK aktivnosti; • aktivacija MAPK aktivnosti; • signalni put G-protein spregnutog receptora; • sinaptička transmisija; • lokomotorno ponašanje; • kalcijumom posredovana signalizacija; • regulacija MAPK kascade; • regulacija senzorne percepcije bola; • regulacija sinaptičke transmisije, glutamatergička; • celularni respons na električni stimulus;
Pregled RNK izražavanja
	podaci
Ortolozi

edit

Metabotropni glutamatni receptor 1 (GRM1) je ljudski gen koji kodira mGluR1 protein.^[1]^[2]^[3]

Funkcija[uredi | uredi kod]

L-glutamat je ekscitatorni neurotransmiter u centralnom nervom sistemu. On aktivira jonotropne i metabotropne glutamatne receptore. Glutamatergična neurotransmisija učestvuje u znatnom broju aspekata normalne moždane funkcije i može da bude poremećena u slučajevima mnogih neuropatoloških oboljenja. Metabotropni glutamatni receptori su familija G protein spregnutih receptora, koja se deli u tri grupe na osnovu sekventne homologije, mehanizma prenosa signala, i farmakoloških svojstava. Grupa I obuhvata GRM1 i GRM5. Za te receptore je pokazano da aktiviraju fosfolipazu C. U grupi II su GRM2 i GRM3, dok su u grupi III GRM4, GRM6, GRM7 i GRM8. Grupe II i III receptora su vezana za inhibiciju kaskade cikličnog AMP, ali se razlikuju u njihovoj specifičnosti za agoniste. Alternativno splajsne varijante GRM1 gena su opisane, ali odgovarajući proteini pune dužine nisu bili određeni.^[1]

Klinički značaj[uredi | uredi kod]

Mutacije GRM1 gena mogu da doprinesu podložnosti na razvoj melanoma.^[4]

Ligandi[uredi | uredi kod]

Pored ortosternog mesta vezivanja liganda gde se glutamat vezuje, postoje bar još dva alosterna mesta vezivanja na mGluR1 receptoru.^[5] Znatan broj potentnih i specifičnih alosternih liganda – predominantno antagonista/inhibitora je razvijen, mada ortosterni podtip-selektivni ligandi nisu poznati.

JNJ-16259685: visoko potentan, selektivan nekompetitivan antagonist^[6]
R-214,127 i [³H]-analog: selektivni alosterni inhibitor visokog afiniteta^[7]
YM-202,074: selektivni alosterni antagonist visokog afiniteta^[8]
YM-230,888: selektivni alosterni antagonist visokog afiniteta^[9]
YM-298,198 i [³H]-analog: selektivni nekompetitivni antagonist^[10]
FTIDC: selektivni alosterni antagonist/inverzni agonist visokog afiniteta^[11]
A-841,720: potentan nekompetitivni antagonist; manje hmGluR5 vezivanje^[12]
VU-71: potencijator^[5]
Fluorisani oksazol-2-il-amidi 9H-ksanten-9-karboksilne kiseline: oralno dostupni potencijatori^[13]

Reference[uredi | uredi kod]

↑ ^1,0 ^1,1 „Entrez Gene: GRM1 glutamate receptor, metabotropic 1”.
↑ Stephan D, Bon C, Holzwarth JA, Galvan M, Pruss RM (1996). „Human metabotropic glutamate receptor 1: mRNA distribution, chromosome localization and functional expression of two splice variants”. Neuropharmacology 35 (12): 1649–60. DOI:10.1016/S0028-3908(96)00108-6. PMID 9076744.
↑ Makoff AJ, Phillips T, Pilling C, Emson P (September 1997). „Expression of a novel splice variant of human mGluR1 in the cerebellum”. Neuroreport 8 (13): 2943–7. DOI:10.1097/00001756-199709080-00027. PMID 9376535.
↑ Ortiz P, Vanaclocha F, López-Bran E, Esquivias JI, López-Estebaranz JL, Martín-González M, Arrue I, García-Romero D, Ochoa C, González-Perez A, Ruiz A, Real LM (November 2007). „Genetic analysis of the GRM1 gene in human melanoma susceptibility”. Eur. J. Hum. Genet. 15 (11): 1176–82. DOI:10.1038/sj.ejhg.5201887. PMID 17609672.
↑ ^5,0 ^5,1 Hemstapat K, de Paulis T, Chen Y, et al. (2006). „A novel class of positive allosteric modulators of metabotropic glutamate receptor subtype 1 interact with a site distinct from that of negative allosteric modulators”. Mol. Pharmacol. 70 (2): 616–26. DOI:10.1124/mol.105.021857. PMID 16645124.
↑ Lavreysen H, Wouters R, Bischoff F, et al. (2004). „JNJ16259685, a highly potent, selective and systemically active mGlu1 receptor antagonist”. Neuropharmacology 47 (7): 961–72. DOI:10.1016/j.neuropharm.2004.08.007. PMID 15555631.
↑ Lavreysen H, Janssen C, Bischoff F, Langlois X, Leysen JE, Lesage AS (2003). „[3HR214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists”]. Mol. Pharmacol. 63 (5): 1082–93. DOI:10.1124/mol.63.5.1082. PMID 12695537. ^{[mrtav link]}
↑ Kohara A, Takahashi M, Yatsugi S, et al. (2008). „Neuroprotective effects of the selective type 1 metabotropic glutamate receptor antagonist YM-202074 in rat stroke models”. Brain Res. 1191: 168–79. DOI:10.1016/j.brainres.2007.11.035. PMID 18164695.
↑ Kohara A, Nagakura Y, Kiso T, et al. (2007). „Antinociceptive profile of a selective metabotropic glutamate receptor 1 antagonist YM-230888 in chronic pain rodent models”. Eur. J. Pharmacol. 571 (1): 8–16. DOI:10.1016/j.ejphar.2007.05.030. PMID 17597604.
↑ Kohara A, Toya T, Tamura S, et al. (2005). „Radioligand binding properties and pharmacological characterization of 6-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-298198), a high-affinity, selective, and noncompetitive antagonist of metabotropic glutamate receptor type 1”. J. Pharmacol. Exp. Ther. 315 (1): 163–9. DOI:10.1124/jpet.105.087171. PMID 15976016.
↑ Suzuki G, Kimura T, Satow A, et al. (2007). „Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide (FTIDC)”. J. Pharmacol. Exp. Ther. 321 (3): 1144–53. DOI:10.1124/jpet.106.116574. PMID 17360958.
↑ El-Kouhen O, Lehto SG, Pan JB, et al. (2006). „Blockade of mGluR1 receptor results in analgesia and disruption of motor and cognitive performances: effects of A-841720, a novel non-competitive mGluR1 receptor antagonist”. Br. J. Pharmacol. 149 (6): 761–74. DOI:10.1038/sj.bjp.0706877. PMC 2014656. PMID 17016515.
↑ Vieira E, Huwyler J, Jolidon S, Knoflach F, Mutel V, Wichmann J (2009). „Fluorinated 9H-xanthene-9-carboxylic acid oxazol-2-yl-amides as potent, orally available mGlu1 receptor enhancers”. Bioorg. Med. Chem. Lett. 19 (6): 1666–9. DOI:10.1016/j.bmcl.2009.01.108. PMID 19233648.

Literatura[uredi | uredi kod]

Bockaert J, Pin JP (1999). „Molecular tinkering of G protein-coupled receptors: an evolutionary success.”. EMBO J. 18 (7): 1723–9. DOI:10.1093/emboj/18.7.1723. PMC 1171258. PMID 10202136.
King JE, Eugenin EA, Buckner CM, Berman JW (2006). „HIV tat and neurotoxicity.”. Microbes Infect. 8 (5): 1347–57. DOI:10.1016/j.micinf.2005.11.014. PMID 16697675.
Desai MA, Burnett JP, Mayne NG, Schoepp DD (1995). „Cloning and expression of a human metabotropic glutamate receptor 1 alpha: enhanced coupling on co-transfection with a glutamate transporter.”. Mol. Pharmacol. 48 (4): 648–57. PMID 7476890.
Scherer SW, Duvoisin RM, Kuhn R, et al. (1997). „Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q.”. Genomics 31 (2): 230–3. DOI:10.1006/geno.1996.0036. PMID 8824806.
Brakeman PR, Lanahan AA, O'Brien R, et al. (1997). „Homer: a protein that selectively binds metabotropic glutamate receptors.”. Nature 386 (6622): 284–8. DOI:10.1038/386284a0. PMID 9069287.
Stephan D, Bon C, Holzwarth JA, et al. (1997). „Human metabotropic glutamate receptor 1: mRNA distribution, chromosome localization and functional expression of two splice variants.”. Neuropharmacology 35 (12): 1649–60. DOI:10.1016/S0028-3908(96)00108-6. PMID 9076744.
Makoff AJ, Phillips T, Pilling C, Emson P (1997). „Expression of a novel splice variant of human mGluR1 in the cerebellum.”. Neuroreport 8 (13): 2943–7. DOI:10.1097/00001756-199709080-00027. PMID 9376535.
Francesconi A, Duvoisin RM (1998). „Role of the second and third intracellular loops of metabotropic glutamate receptors in mediating dual signal transduction activation.”. J. Biol. Chem. 273 (10): 5615–24. DOI:10.1074/jbc.273.10.5615. PMID 9488690.
Okamoto T, Sekiyama N, Otsu M, et al. (1998). „Expression and purification of the extracellular ligand binding region of metabotropic glutamate receptor subtype 1.”. J. Biol. Chem. 273 (21): 13089–96. DOI:10.1074/jbc.273.21.13089. PMID 9582347.
Snow BE, Hall RA, Krumins AM, et al. (1998). „GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain.”. J. Biol. Chem. 273 (28): 17749–55. DOI:10.1074/jbc.273.28.17749. PMID 9651375.
Xiao B, Tu JC, Petralia RS, et al. (1998). „Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins.”. Neuron 21 (4): 707–16. DOI:10.1016/S0896-6273(00)80588-7. PMID 9808458.
Tu JC, Xiao B, Yuan JP, et al. (1998). „Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors.”. Neuron 21 (4): 717–26. DOI:10.1016/S0896-6273(00)80589-9. PMID 9808459.
Ciruela F, Robbins MJ, Willis AC, McIlhinney RA (1999). „Interactions of the C terminus of metabotropic glutamate receptor type 1alpha with rat brain proteins: evidence for a direct interaction with tubulin.”. J. Neurochem. 72 (1): 346–54. DOI:10.1046/j.1471-4159.1999.0720346.x. PMID 9886087.
Robbins MJ, Ciruela F, Rhodes A, McIlhinney RA (1999). „Characterization of the dimerization of metabotropic glutamate receptors using an N-terminal truncation of mGluR1alpha.”. J. Neurochem. 72 (6): 2539–47. DOI:10.1046/j.1471-4159.1999.0722539.x. PMID 10349865.
Mody N, Hermans E, Nahorski SR, Challiss RA (1999). „Inhibition of N-linked glycosylation of the human type 1alpha metabotropic glutamate receptor by tunicamycin: effects on cell-surface receptor expression and function.”. Neuropharmacology 38 (10): 1485–92. DOI:10.1016/S0028-3908(99)00099-4. PMID 10530810.
Francesconi A, Duvoisin RM (2000). „Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: selective desensitization of the inositol trisphosphate/Ca2+ pathway by phosphorylation of the receptor-G protein-coupling domain.”. Proc. Natl. Acad. Sci. U.S.A. 97 (11): 6185–90. DOI:10.1073/pnas.97.11.6185. PMC 18579. PMID 10823959.
Ganesh S, Amano K, Yamakawa K (2000). „Assignment of the gene GRM1 coding for metabotropic glutamate receptor 1 to human chromosome band 6q24 by in situ hybridization.”. Cytogenet. Cell Genet. 88 (3–4): 314–5. DOI:10.1159/000015517. PMID 10828618.
Ray K, Hauschild BC (2000). „Cys-140 is critical for metabotropic glutamate receptor-1 dimerization”. J. Biol. Chem. 275 (44): 34245–51. DOI:10.1074/jbc.M005581200. PMID 10945991.
Hartley JL, Temple GF, Brasch MA (2001). „DNA cloning using in vitro site-specific recombination”. Genome Res. 10 (11): 1788–95. DOI:10.1101/gr.143000. PMC 310948. PMID 11076863.

Vidi još[uredi | uredi kod]

Metabotropni glutamatni receptor

Spoljašnje veze[uredi | uredi kod]

„Metabotropic Glutamate Receptors: mGlu₁”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-03.

[entrez-1] 1,0 ^1,1 „Entrez Gene: GRM1 glutamate receptor, metabotropic 1”.

[pmid9076744-2] Stephan D, Bon C, Holzwarth JA, Galvan M, Pruss RM (1996). „Human metabotropic glutamate receptor 1: mRNA distribution, chromosome localization and functional expression of two splice variants”. Neuropharmacology 35 (12): 1649–60. DOI:10.1016/S0028-3908(96)00108-6. PMID 9076744.

[pmid9376535-3] Makoff AJ, Phillips T, Pilling C, Emson P (September 1997). „Expression of a novel splice variant of human mGluR1 in the cerebellum”. Neuroreport 8 (13): 2943–7. DOI:10.1097/00001756-199709080-00027. PMID 9376535.

[pmid17609672-4] Ortiz P, Vanaclocha F, López-Bran E, Esquivias JI, López-Estebaranz JL, Martín-González M, Arrue I, García-Romero D, Ochoa C, González-Perez A, Ruiz A, Real LM (November 2007). „Genetic analysis of the GRM1 gene in human melanoma susceptibility”. Eur. J. Hum. Genet. 15 (11): 1176–82. DOI:10.1038/sj.ejhg.5201887. PMID 17609672.

[Hemstapat_K,_de_Paulis_T,_Chen_Y,_et_al._2006_616–26-5] 5,0 ^5,1 Hemstapat K, de Paulis T, Chen Y, et al. (2006). „A novel class of positive allosteric modulators of metabotropic glutamate receptor subtype 1 interact with a site distinct from that of negative allosteric modulators”. Mol. Pharmacol. 70 (2): 616–26. DOI:10.1124/mol.105.021857. PMID 16645124.

[6] Lavreysen H, Wouters R, Bischoff F, et al. (2004). „JNJ16259685, a highly potent, selective and systemically active mGlu1 receptor antagonist”. Neuropharmacology 47 (7): 961–72. DOI:10.1016/j.neuropharm.2004.08.007. PMID 15555631.

[7] Lavreysen H, Janssen C, Bischoff F, Langlois X, Leysen JE, Lesage AS (2003). „[3HR214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists”]. Mol. Pharmacol. 63 (5): 1082–93. DOI:10.1124/mol.63.5.1082. PMID 12695537. ^{[mrtav link]}

[8] Kohara A, Takahashi M, Yatsugi S, et al. (2008). „Neuroprotective effects of the selective type 1 metabotropic glutamate receptor antagonist YM-202074 in rat stroke models”. Brain Res. 1191: 168–79. DOI:10.1016/j.brainres.2007.11.035. PMID 18164695.

[9] Kohara A, Nagakura Y, Kiso T, et al. (2007). „Antinociceptive profile of a selective metabotropic glutamate receptor 1 antagonist YM-230888 in chronic pain rodent models”. Eur. J. Pharmacol. 571 (1): 8–16. DOI:10.1016/j.ejphar.2007.05.030. PMID 17597604.

[10] Kohara A, Toya T, Tamura S, et al. (2005). „Radioligand binding properties and pharmacological characterization of 6-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-298198), a high-affinity, selective, and noncompetitive antagonist of metabotropic glutamate receptor type 1”. J. Pharmacol. Exp. Ther. 315 (1): 163–9. DOI:10.1124/jpet.105.087171. PMID 15976016.

[11] Suzuki G, Kimura T, Satow A, et al. (2007). „Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide (FTIDC)”. J. Pharmacol. Exp. Ther. 321 (3): 1144–53. DOI:10.1124/jpet.106.116574. PMID 17360958.

[12] El-Kouhen O, Lehto SG, Pan JB, et al. (2006). „Blockade of mGluR1 receptor results in analgesia and disruption of motor and cognitive performances: effects of A-841720, a novel non-competitive mGluR1 receptor antagonist”. Br. J. Pharmacol. 149 (6): 761–74. DOI:10.1038/sj.bjp.0706877. PMC 2014656. PMID 17016515.

[pmid19233648-13] Vieira E, Huwyler J, Jolidon S, Knoflach F, Mutel V, Wichmann J (2009). „Fluorinated 9H-xanthene-9-carboxylic acid oxazol-2-yl-amides as potent, orally available mGlu1 receptor enhancers”. Bioorg. Med. Chem. Lett. 19 (6): 1666–9. DOI:10.1016/j.bmcl.2009.01.108. PMID 19233648.

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Metabotropni glutamatni receptor 1

Sadržaj

Funkcija[uredi | uredi kod]

Klinički značaj[uredi | uredi kod]

Ligandi[uredi | uredi kod]

Reference[uredi | uredi kod]

Literatura[uredi | uredi kod]

Vidi još[uredi | uredi kod]

Spoljašnje veze[uredi | uredi kod]

Navigacija

Metabotropni glutamatni receptor 1

Funkcija[uredi | uredi kod]

Klinički značaj[uredi | uredi kod]

Ligandi[uredi | uredi kod]

Reference[uredi | uredi kod]

Literatura[uredi | uredi kod]

Vidi još[uredi | uredi kod]

Spoljašnje veze[uredi | uredi kod]

Navigacija

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