Metabotropic glutamate receptor 4
Appearance
(Redirected fromGRM4)
Metabotropic glutamate receptor 4is aproteinthat in humans is encoded by theGRM4gene.[5][6][7]
Together with GRM6, GRM7 and GRM8 it belongs togroup IIIof themetabotropic glutamate receptorfamily. Group III receptors are linked to the inhibition of the cyclic AMP cascade.[7] Activation of GRM4 has potential therapeutic benefits in the treatment ofparkinson's disease.Splice variant"taste-GRM4" is involved in the perception ofumamitaste.[8]
Ligands
[edit]Orthosteric
[edit]- Cinnabarinic acid,a tryptophan metabolite[9]
- LSP1-2111: agonist[10]
- LSP4-2022: agonist[11]
- LSP2-9166:mixed agonist at mGluR4and mGluR7
Positive allosteric modulators (PAMs)
[edit]- Foliglurax(PXT-002331, DT-1687)
- Tricyclic thiazolopyrazole derivative 22a: EC50= 9 nM, Emax= 120%[12]
- ML-128:EC50= 240 nM, Emax= 182%[13][14]
- VU0652957 (AP-472) (Valiglurax)[15]
- VU-0418506[16][17]
- VU-001171: EC50= 650 nM, Emax= 141%, 36-fold shift[18]
- VU-0155041: subtype-selective PAM, intrinsic allosteric agonist activity, robust in-vivo activity[19]
- PHCCC:PAM of mGluR4, negative allosteric modulator ofmGluR1,[20]direct agonist atmGluR6[21]
References
[edit]- ^abcGRCh38: Ensembl release 89: ENSG00000124493–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000063239–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^Makoff A, Lelchuk R, Oxer M, Harrington K, Emson P (April 1996). "Molecular characterization and localization of human metabotropic glutamate receptor type 4".Brain Research. Molecular Brain Research.37(1–2): 239–248.doi:10.1016/0169-328X(95)00321-I.PMID8738157.
- ^Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR, et al. (January 1998). "Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells".Brain Research. Molecular Brain Research.53(1–2): 88–97.doi:10.1016/S0169-328X(97)00277-5.PMID9473604.
- ^ab"Entrez Gene: GRM4 glutamate receptor, metabotropic 4".
- ^Chaudhari N, Landin AM, Roper SD (February 2000). "A metabotropic glutamate receptor variant functions as a taste receptor".Nature Neuroscience.3(2): 113–119.doi:10.1038/72053.PMID10649565.S2CID16650588.
- ^Fazio F, Lionetto L, Molinaro G, Bertrand HO, Acher F, Ngomba RT, et al. (May 2012). "Cinnabarinic acid, an endogenous metabolite of the kynurenine pathway, activates type 4 metabotropic glutamate receptors".Molecular Pharmacology.81(5): 643–656.doi:10.1124/mol.111.074765.PMID22311707.S2CID6735807.
- ^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): 627–634.doi:10.1016/j.neuropharm.2010.08.008.PMID20713068.S2CID5171741.
- ^Goudet C, Vilar B, Courtiol T, Deltheil T, Bessiron T, Brabet I, et al. (April 2012)."A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential".FASEB Journal.26(4): 1682–1693.doi:10.1096/fj.11-195941.PMID22223752.S2CID22662090.
- ^Hong SP, Liu KG, Ma G, Sabio M, Uberti MA, Bacolod MD, et al. (July 2011). "Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators".Journal of Medicinal Chemistry.54(14): 5070–5081.doi:10.1021/jm200290z.PMID21688779.
- ^Hopkins CR, Niswender CM, Lewis LM, Weaver CD, Lindsley CW (2010). "Discovery of a potent, selective and in vivo active mGluR4 positive allosteric modulator".Probe Reports from the NIH Molecular Libraries Program [Internet].PMID21433377.
- ^Engers DW, Niswender CM, Weaver CD, Jadhav S, Menon UN, Zamorano R, 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)".Journal of Medicinal Chemistry.52(14): 4115–4118.doi:10.1021/jm9005065.PMC2765192.PMID19469556.
- ^Panarese JD, Engers DW, Wu YJ, Bronson JJ, Macor JE, Chun A, et al. (March 2019)."Discovery of VU2957 (Valiglurax): An mGlu4Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease ".ACS Medicinal Chemistry Letters.10(3): 255–260.doi:10.1021/acsmedchemlett.8b00426.PMC6421540.PMID30891122.
- ^Niswender CM, Jones CK, Lin X, Bubser M, Thompson Gray A, Blobaum AL, et al. (September 2016)."Development and Antiparkinsonian Activity of VU0418506, a Selective Positive Allosteric Modulator of Metabotropic Glutamate Receptor 4 Homomers without Activity at mGlu2/4 Heteromers".ACS Chemical Neuroscience.7(9): 1201–1211.doi:10.1021/acschemneuro.6b00036.PMC5073817.PMID27441572.
- ^Engers DW, Blobaum AL, Gogliotti RD, Cheung YY, Salovich JM, Garcia-Barrantes PM, et al. (September 2016)."Discovery, Synthesis, and Preclinical Characterization of N-(3-Chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506), a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4)".ACS Chemical Neuroscience.7(9): 1192–1200.doi:10.1021/acschemneuro.6b00035.PMC5031509.PMID27075300.
- ^Williams R, Niswender CM, Luo Q, Le U, Conn PJ, Lindsley CW (February 2009)."Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead".Bioorganic & Medicinal Chemistry Letters.19(3): 962–966.doi:10.1016/j.bmcl.2008.11.104.PMC3787871.PMID19097893.
- ^Niswender CM, Johnson KA, Weaver CD, Jones CK, Xiang Z, Luo Q, et al. (November 2008)."Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4".Molecular Pharmacology.74(5): 1345–1358.doi:10.1124/mol.108.049551.PMC2574552.PMID18664603.
- ^Watkins JC, Jane DE (January 2006)."The glutamate story".British Journal of Pharmacology.147(Suppl 1): S100–S108.doi:10.1038/sj.bjp.0706444.PMC1760733.PMID16402093.
- ^Beqollari D, Kammermeier PJ (July 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.PMID18593581.
Further reading
[edit]- Flor PJ, Lukic S, Rüegg D, Leonhardt T, Knöpfel T, Kuhn R (February 1995). "Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 4".Neuropharmacology.34(2): 149–155.doi:10.1016/0028-3908(94)00149-M.PMID7617140.S2CID31399907.
- Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC (January 1996)."Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q".Genomics.31(2): 230–233.doi:10.1006/geno.1996.0036.PMID8824806.
- Gomeza J, Mary S, Brabet I, Parmentier ML, Restituito S, Bockaert J, et al. (October 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".Molecular Pharmacology.50(4): 923–930.PMID8863838.
- Fu M, Wang C, Reutens AT, Wang J, Angeletti RH, Siconolfi-Baez L, et al. (July 2000)."p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation".The Journal of Biological Chemistry.275(27): 20853–20860.doi:10.1074/jbc.M000660200.PMID10779504.
- 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".Cytogenetics and Cell Genetics.88(3–4): 210.doi:10.1159/000015551.PMID10828590.S2CID85055574.
- Ohtsuki T, Toru M, Arinami T (June 2001). "Mutation screening of the metabotropic glutamate receptor mGluR4 (GRM4) gene in patients with schizophrenia".Psychiatric Genetics.11(2): 79–83.doi:10.1097/00041444-200106000-00004.PMID11525421.S2CID752064.
- Erdemir T, Bilican B, Oncel D, Goding CR, Yavuzer U (January 2002)."DNA damage-dependent interaction of the nuclear matrix protein C1D with Translin-associated factor X (TRAX)".Journal of Cell Science.115(Pt 1): 207–216.doi:10.1242/jcs.115.1.207.PMID11801738.
- Collard CD, Park KA, Montalto MC, Alapati S, Buras JA, Stahl GL, et al. (April 2002)."Neutrophil-derived glutamate regulates vascular endothelial barrier function".The Journal of Biological Chemistry.277(17): 14801–14811.doi:10.1074/jbc.M110557200.PMID11847215.
- Enz R (March 2002)."The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7".FEBS Letters.514(2–3): 184–188.Bibcode:2002FEBSL.514..184E.doi:10.1016/S0014-5793(02)02361-X.PMID11943148.S2CID44474808.
- Gaughan L, Logan IR, Cook S, Neal DE, Robson CN (July 2002)."Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor".The Journal of Biological Chemistry.277(29): 25904–25913.doi:10.1074/jbc.M203423200.PMID11994312.
- Iacovelli L, Capobianco L, Iula M, Di Giorgi Gerevini V, Picascia A, Blahos J, et al. (May 2004). "Regulation of mGlu4 metabotropic glutamate receptor signaling by type-2 G-protein coupled receptor kinase (GRK2)".Molecular Pharmacology.65(5): 1103–1110.doi:10.1124/mol.65.5.1103.PMID15102938.
- Hermit MB, Greenwood JR, Bräuner-Osborne H (August 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".The Journal of Biological Chemistry.279(33): 34811–34817.doi:10.1074/jbc.M404109200.PMID15184361.
- Yoo BC, Jeon E, Hong SH, Shin YK, Chang HJ, Park JG (June 2004)."Metabotropic glutamate receptor 4-mediated 5-Fluorouracil resistance in a human colon cancer cell line".Clinical Cancer Research.10(12 Pt 1): 4176–4184.doi:10.1158/1078-0432.CCR-1114-03.PMID15217955.
- Chang HJ, Yoo BC, Lim SB, Jeong SY, Kim WH, Park JG (May 2005)."Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its prognostic significance".Clinical Cancer Research.11(9): 3288–3295.doi:10.1158/1078-0432.CCR-04-1912.PMID15867225.
- Mathiesen JM, Ramirez MT (June 2006)."The metabotropic glutamate receptor 4 is internalized and desensitized upon protein kinase C activation".British Journal of Pharmacology.148(3): 279–290.doi:10.1038/sj.bjp.0706733.PMC1751557.PMID16582932.
- Iacovelli L, Arcella A, Battaglia G, Pazzaglia S, Aronica E, Spinsanti P, et al. (August 2006)."Pharmacological activation of mGlu4 metabotropic glutamate receptors inhibits the growth of medulloblastomas".The Journal of Neuroscience.26(32): 8388–8397.doi:10.1523/JNEUROSCI.2285-06.2006.PMC6673797.PMID16899734.
This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.