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 uredi

Ortosterni uredi

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

Pozitivni alosterni modulatori (PAM) uredi

3d model jedinjenja 22a (Hong 2011)

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 uredi

↑ 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 uredi

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.
Chang HJ, Yoo BC, Lim SB, et al. (2005). „Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its prognostic significance.”. Clin. Cancer Res. 11 (9): 3288–95. DOI:10.1158/1078-0432.CCR-04-1912. PMID 15867225.
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 uredi

„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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