Metabotropni glutamatni receptor 4

Glutamatni receptor, metabotropni 4
Identifikatori
Simboli	GRM4; GPRC1D; MGLUR4; mGlu4
Vanjski ID	OMIM: 604100 MGI: 1351341 HomoloGene: 20230 IUPHAR: mGlu4 GeneCards: GRM4 Gene
Ontologija gena
Molekularna funkcija	• aktivnost prenosa signala; • receptorska aktivnost; • aktivnost G protein spregnutog receptora; • aktivnost glutamatnog receptora;
Celularna komponenta	• intracelularni; • ćelijska membrana; • integralno sa ćelijskom membranom; • integralno sa membranom; • ciytoplazmatične vezikule;
Biološki proces	• aktivacija MAPK aktivnosti; • signalni put G protein spregnutog receptora; • inhibicija aktivnosti adenilat ciklaze signalnim putem G protein spregnutog glutamatnog receptora; • sinaptička transmisija; • sekrecija neurotransmitera; • pozitivna regulacija MAPK kaskade; • neuroprotekcija;
Pregled RNK izražavanja
	podaci
Ortolozi

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Metabotropni glutamatni receptor 4 je protein koji je kod ljudi kodiran GRM4 genom.^[1]^[2]^[3]

Ovaj protein zajedno sa GRM6, GRM7 i GRM8 pripada grupi III familije metabotropnih glutamatnih receptora. Grupa III receptora je vezana za inhibiciju kaskade cikličnog AMP.^[3] Aktivacija GRM4 je potencijao terapeutski korisna u tretmanu Parkinsonove bolesti.

Ligandi

Ortosterni

LSP1-2111^[4], LSP1-3081: agonisti

Pozitivni alosterni modulatori (PAM)

Triciklični tiazolopirazolni derivati jedinjenja 22a: EC₅₀ = 9 nM, E_max = 120%^[5]
ML-128: EC₅₀ = 240 nM, E_max = 182%^[6]^[7]
VU-001171: EC₅₀ = 650 nM, E_max = 141%^[8]
VU-0155041: podtip-selektivni PAM agonist sa robastnom in vivo aktivnošću^[9]
PHCCC: PAM mGluR4, negativni alosterni modulator mGluR1,^[10] direktni agonist mGluR6^[11]

Reference

↑ Makoff A, Lelchuk R, Oxer M, Harrington K, Emson P (Dec 1996). „Molecular characterization and localization of human metabotropic glutamate receptor type 4”. Brain Res Mol Brain Res 37 (1-2): 239–48. DOI:10.1016/0169-328X(95)00321-I. PMID 8738157.
↑ Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR Jr, Johnson BG, Schoepp DD, Belagaje RM (Apr 1998). „Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells”. Brain Res Mol Brain Res 53 (1-2): 88–97. DOI:10.1016/S0169-328X(97)00277-5. PMID 9473604.
↑ ^3,0 ^3,1 „Entrez Gene: GRM4 glutamate receptor, metabotropic 4”.
↑ Wierońska JM, Stachowicz K, Pałucha-Poniewiera A, Acher F, Brański P, Pilc A (December 2010). „Metabotropic glutamate receptor 4 novel agonist LSP1-2111 with anxiolytic, but not antidepressant-like activity, mediated by serotonergic and GABAergic systems”. Neuropharmacology 59 (7-8): 627–34. DOI:10.1016/j.neuropharm.2010.08.008. PMID 20713068.
↑ Hong SP, Liu KG, Ma G, et al. (July 2011). „Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators”. J. Med. Chem. 54 (14): 5070–81. DOI:10.1021/jm200290z. PMID 21688779.
↑ Hopkins CR, Niswender CM, Lewis LM, Weaver CD, Lindsley CW. Discovery of a potent, selective and in vivo active mGluR4 positive allosteric modulator. PMID 21433377.
↑ Engers DW, Niswender CM, Weaver CD, et al. (July 2009). „Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)”. J. Med. Chem. 52 (14): 4115–8. DOI:10.1021/jm9005065. PMC 2765192. PMID 19469556.
↑ Williams R, Niswender CM, Luo Q, Le U, Conn PJ, Lindsley CW (2009). „Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead”. Bioorg. Med. Chem. Lett. 19 (3): 962–6. DOI:10.1016/j.bmcl.2008.11.104. PMID 19097893.
↑ Niswender CM, Johnson KA, Weaver CD, et al. (2008). „Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4”. Mol. Pharmacol. 74 (5): 1345–58. DOI:10.1124/mol.108.049551. PMC 2574552. PMID 18664603.
↑ Watkins JC, Jane DE (2006). „The glutamate story”. British Journal of Pharmacology 147 (Suppl 1): S100–8. DOI:10.1038/sj.bjp.0706444. PMC 1760733. PMID 16402093.
↑ Beqollari D, Kammermeier PJ (2008). „The mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide acts as a direct agonist at mGlu(6) receptors”. European Journal of Pharmacology 589 (1-3): 49–52. DOI:10.1016/j.ejphar.2008.06.054. PMID 18593581.

Literatura

Flor PJ, Lukic S, Rüegg D, et al. (1995). „Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 4.”. Neuropharmacology 34 (2): 149–55. DOI:10.1016/0028-3908(94)00149-M. PMID 7617140.
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.
Gomeza J, Mary S, Brabet I, et al. (1996). „Coupling of metabotropic glutamate receptors 2 and 4 to G alpha 15, G alpha 16, and chimeric G alpha q/i proteins: characterization of new antagonists.”. Mol. Pharmacol. 50 (4): 923–30. PMID 8863838.
Fu M, Wang C, Reutens AT, et al. (2000). „p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation.”. J. Biol. Chem. 275 (27): 20853–60. DOI:10.1074/jbc.M000660200. PMID 10779504.
Barbon A, Ferraboli S, Barlati S (2000). „Assignment of the human metabotropic glutamate receptor gene GRM4 to chromosome 6 band p21.3 by radiation hybrid mapping.”. Cytogenet. Cell Genet. 88 (3-4): 210. DOI:10.1159/000015551. PMID 10828590.
Ohtsuki T, Toru M, Arinami T (2002). „Mutation screening of the metabotropic glutamate receptor mGluR4 (GRM4) gene in patients with schizophrenia.”. Psychiatr. Genet. 11 (2): 79–83. DOI:10.1097/00041444-200106000-00004. PMID 11525421.
Erdemir T, Bilican B, Oncel D, et al. (2002). „DNA damage-dependent interaction of the nuclear matrix protein C1D with Translin-associated factor X (TRAX).”. J. Cell. Sci. 115 (Pt 1): 207–16. PMID 11801738.
Collard CD, Park KA, Montalto MC, et al. (2002). „Neutrophil-derived glutamate regulates vascular endothelial barrier function.”. J. Biol. Chem. 277 (17): 14801–11. DOI:10.1074/jbc.M110557200. PMID 11847215.
Enz R (2002). „The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7.”. FEBS Lett. 514 (2-3): 184–8. DOI:10.1016/S0014-5793(02)02361-X. PMID 11943148.
Gaughan L, Logan IR, Cook S, et al. (2002). „Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor.”. J. Biol. Chem. 277 (29): 25904–13. DOI:10.1074/jbc.M203423200. PMID 11994312.
Mungall AJ, Palmer SA, Sims SK, et al. (2003). „The DNA sequence and analysis of human chromosome 6.”. Nature 425 (6960): 805–11. DOI:10.1038/nature02055. PMID 14574404.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). „Complete sequencing and characterization of 21,243 full-length human cDNAs.”. Nat. Genet. 36 (1): 40–5. DOI:10.1038/ng1285. PMID 14702039.
Iacovelli L, Capobianco L, Iula M, et al. (2004). „Regulation of mGlu4 metabotropic glutamate receptor signaling by type-2 G-protein coupled receptor kinase (GRK2).”. Mol. Pharmacol. 65 (5): 1103–10. DOI:10.1124/mol.65.5.1103. PMID 15102938.
Hermit MB, Greenwood JR, Bräuner-Osborne H (2004). „Mutation-induced quisqualic acid and ibotenic acid affinity at the metabotropic glutamate receptor subtype 4: ligand selectivity results from a synergy of several amino acid residues.”. J. Biol. Chem. 279 (33): 34811–7. DOI:10.1074/jbc.M404109200. PMID 15184361.
Yoo BC, Jeon E, Hong SH, et al. (2005). „Metabotropic glutamate receptor 4-mediated 5-Fluorouracil resistance in a human colon cancer cell line.”. Clin. Cancer Res. 10 (12 Pt 1): 4176–84. DOI:10.1158/1078-0432.CCR-1114-03. PMID 15217955.
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Mathiesen JM, Ramirez MT (2006). „The metabotropic glutamate receptor 4 is internalized and desensitized upon protein kinase C activation.”. Br. J. Pharmacol. 148 (3): 279–90. DOI:10.1038/sj.bjp.0706733. PMC 1751557. PMID 16582932.
Iacovelli L, Arcella A, Battaglia G, et al. (2006). „Pharmacological activation of mGlu4 metabotropic glutamate receptors inhibits the growth of medulloblastomas.”. J. Neurosci. 26 (32): 8388–97. DOI:10.1523/JNEUROSCI.2285-06.2006. PMID 16899734.

Spoljašnje veze

„Metabotropic Glutamate Receptors: mGlu₄”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2013-12-03.

[pmid8738157-1] Makoff A, Lelchuk R, Oxer M, Harrington K, Emson P (Dec 1996). „Molecular characterization and localization of human metabotropic glutamate receptor type 4”. Brain Res Mol Brain Res 37 (1-2): 239–48. DOI:10.1016/0169-328X(95)00321-I. PMID 8738157.

[pmid9473604-2] Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR Jr, Johnson BG, Schoepp DD, Belagaje RM (Apr 1998). „Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells”. Brain Res Mol Brain Res 53 (1-2): 88–97. DOI:10.1016/S0169-328X(97)00277-5. PMID 9473604.

[entrez-3] 3,0 ^3,1 „Entrez Gene: GRM4 glutamate receptor, metabotropic 4”.

[4] Wierońska JM, Stachowicz K, Pałucha-Poniewiera A, Acher F, Brański P, Pilc A (December 2010). „Metabotropic glutamate receptor 4 novel agonist LSP1-2111 with anxiolytic, but not antidepressant-like activity, mediated by serotonergic and GABAergic systems”. Neuropharmacology 59 (7-8): 627–34. DOI:10.1016/j.neuropharm.2010.08.008. PMID 20713068.

[5] Hong SP, Liu KG, Ma G, et al. (July 2011). „Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators”. J. Med. Chem. 54 (14): 5070–81. DOI:10.1021/jm200290z. PMID 21688779.

[6] Hopkins CR, Niswender CM, Lewis LM, Weaver CD, Lindsley CW. Discovery of a potent, selective and in vivo active mGluR4 positive allosteric modulator. PMID 21433377.

[pmid19469556-7] Engers DW, Niswender CM, Weaver CD, et al. (July 2009). „Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)”. J. Med. Chem. 52 (14): 4115–8. DOI:10.1021/jm9005065. PMC 2765192. PMID 19469556.

[pmid19097893-8] Williams R, Niswender CM, Luo Q, Le U, Conn PJ, Lindsley CW (2009). „Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead”. Bioorg. Med. Chem. Lett. 19 (3): 962–6. DOI:10.1016/j.bmcl.2008.11.104. PMID 19097893.

[9] Niswender CM, Johnson KA, Weaver CD, et al. (2008). „Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4”. Mol. Pharmacol. 74 (5): 1345–58. DOI:10.1124/mol.108.049551. PMC 2574552. PMID 18664603.

[10] Watkins JC, Jane DE (2006). „The glutamate story”. British Journal of Pharmacology 147 (Suppl 1): S100–8. DOI:10.1038/sj.bjp.0706444. PMC 1760733. PMID 16402093.

[11] Beqollari D, Kammermeier PJ (2008). „The mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide acts as a direct agonist at mGlu(6) receptors”. European Journal of Pharmacology 589 (1-3): 49–52. DOI:10.1016/j.ejphar.2008.06.054. PMID 18593581.

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