Metabotropic glutamate receptor 5

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Metabotropic glutamate receptor 5
other names

mGluR5

Properties of human protein
Mass / length primary structure 1,212 amino acids , 132,469 Da
Identifier
External IDs
Orthologue (human)
Entrez 2915
Ensemble ENSG00000168959
UniProt P41594
Refseq (mRNA) NM_000842.4
Refseq (protein) NP_000833.1
PubMed search 2915

Metabotropic glutamate receptor 5 (GRM 5, mGluR5) is a protein from the group of metabotropic glutamate receptors .

properties

The metabotropic glutamate receptor 5 is a G protein-coupled receptor . Together with mGluR1 it forms group I of the metabotropic glutamate receptors. After binding of glutamate , a change in conformation takes place , which causes signal transduction via G proteins (from the G q family ). As a result, phospholipase C is activated, which leads to the accumulation of IP 3 and diacylglycerol (DAG) inside the cell. About IP 3 receptors it comes to the release of calcium ions from the endoplasmic reticulum , whereas DAG especially the protein kinase C activates. The metabotropic glutamate receptor 5 has disulfide bridges and is glycosylated , methylated and phosphorylated . The metabotropic glutamate receptor 5 is involved in synaptic plasticity .

Ligands

Agonist

  • CHPG (2-amino-2- (2-chloro-5-hydroxyphenyl) acetic acid)

Antagonists

Positive allosteric modulators

  • ADX-47273
  • CPPHA
  • VU-29: K i = 244 nM, EC 50 = 9.0 nM; VU-36: K i = 95 nM, EC 50 = 10.6 nM
  • VU-1545: K i = 156 nM, EC 50 = 9.6 nM
  • CDPPB (3-cyano-N- (1,3-diphenyl-1H-pyrazol-5-yl) benzamide)
  • DFB (1- (3-fluorophenyl) -N - ((3-fluorophenyl) methylideneamino) methanimine)

Orthosteric antagonist

Negative allosteric modulators

Individual evidence

  1. ↑ a b c GRM5 - Metabotropic glutamate receptor 5 precursor - Homo sapiens (Human) - GRM5 gene & protein. In: uniprot.org. October 10, 2018, accessed November 6, 2018 .
  2. ↑ David Amaral: Autism Spectrum Disorders. Oxford University Press, 2011, ISBN 978-0-199-70747-8 , p. 806.
  3. ↑ Liu F, Grauer S, Kelley C, Navarra R, Graf R, Zhang G, Atkinson PJ, Popiolek M, Wantuch C, Khawaja X, Smith D, Olsen M, Kouranova E, Lai M, Pruthi F, Pulicicchio C, Day M, Gilbert A, Pausch MH, Brandon NJ, Beyer CE, Comery TA, Logue S, Rosenzweig-Lipson S, Marquis KL: ADX47273 [S- (4-fluoro-phenyl) - {3- [3- (4-fluoro -phenyl) - [1,2,4] -oxadiazol-5-yl] -piperidin-1-yl} -methanone]: a novel metabotropic glutamate receptor 5-selective positive allosteric modulator with preclinical antipsychotic-like and procognitive activities . In: The Journal of Pharmacology and Experimental Therapeutics . 327, No. 3, December 2008, pp. 827-39. doi : 10.1124 / jpet.108.136580 . PMID 18753411 .
  4. ↑ Zhao Z, Wisnoski DD, O'Brien JA, Lemaire W, Williams DL, Jacobson MA, Wittman M, Ha SN, Schaffhauser H, Sur C, Pettibone DJ, Duggan ME, Conn PJ, Hartman GD, Lindsley CW: Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA . In: Bioorganic & Medicinal Chemistry Letters . 17, No. 5, March 2007, pp. 1386-91. doi : 10.1016 / j.bmcl.2006.11.081 . PMID 17210250 .
  5. ^ O'Brien JA, Lemaire W, Wittmann M, Jacobson MA, Ha SN, Wisnoski DD, Lindsley CW, Schaffhauser HJ, Rowe B, Sur C, Duggan ME, Pettibone DJ, Conn PJ, Williams DL: A novel selective allosteric modulator potentiates the activity of native metabotropic glutamate receptor subtype 5 in rat forebrain . In: The Journal of Pharmacology and Experimental Therapeutics . 309, No. 2, May 2004, pp. 568-77. doi : 10.1124 / jpet.103.061747 . PMID 14747613 .
  6. ↑ Chen Y, Nong Y, Goudet C, Hemstapat K, de Paulis T, Pin JP, Conn PJ: Interaction of novel positive allosteric modulators of metabotropic glutamate receptor 5 with the negative allosteric antagonist site is required for potentiation of receptor responses . In: Molecular Pharmacology . 71, No. 5, May 2007, pp. 1389-98. doi : 10.1124 / mol.106.032425 . PMID 17303702 .
  7. Jump up ↑ de Paulis T, Hemstapat K, Chen Y, Zhang Y, Saleh S, Alagille D, Baldwin RM, Tamagnan GD, Conn PJ: Substituent effects of N- (1,3-diphenyl-1H-pyrazol-5-yl) benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat cortical astrocytes . In: Journal of Medicinal Chemistry . 49, No. 11, June 2006, pp. 3332-44. doi : 10.1021 / jm051252j . PMID 16722652 .
  8. ↑ Kinney GG, O'Brien JA, Lemaire W, Burno M, Bickel DJ, Clements MK, Chen TB, Wisnoski DD, Lindsley CW, Tiller PR, Smith S, Jacobson MA, Sur C, Duggan ME, Pettibone DJ, Conn PJ , Williams DL: A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models . In: The Journal of Pharmacology and Experimental Therapeutics . 313, No. 1, April 2005, pp. 199-206. doi : 10.1124 / jpet.104.079244 . PMID 15608073 .
  9. ↑ Silverman JL, Smith DG, Rizzo SJ, Karras MN, Turner SM, Tolu SS, Bryce DK, Smith DL, Fonseca K, Ring RH, Crawley JN: Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism . In: Science Translational Medicine . 4, No. 131, April 2012, p. 131ra51. doi : 10.1126 / scitranslmed.3003501 . PMID 22539775 . PMC 4904784 (free full text).