Izvorni kod stranice Metabotropni glutamatni receptor 3

{{PBB|geneid=2913}}
'''Metabotropni glutamatni receptor 3''' je [[protein]] koji je kod ljudi kodiran {{Gene|GRM3}} [[gen]]om.<ref name="pmid8824806">{{cite journal | author = Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC | title = Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q | journal = Genomics | volume = 31 | issue = 2 | pages = 230–3 | year = 1997 | month = Mar | pmid = 8824806 | pmc =  | doi = 10.1006/geno.1996.0036 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: GRM3 glutamate receptor, metabotropic 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2913| accessdate = }}</ref>

<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title = 
| summary_text = [[Glutaminska kiselina|L-glutamat]] je jedan od glavnih ekscitatornih [[neurotransmiter]]a [[centralni nervni sistem|centralnog nervnog sistema]]. On aktivira jonotropne i metabotropne glutamatne receptore. Glutamatergična neurotransmisija učestvuje u većini aspekata normalne moždane funkcije. Ona može da bude modifikovana mnogim neuropatološkim uslovima. Metabotropini glutamatni receptori su familija [[G protein spregnuti receptor|G protein spregnutih receptora]], koji se dele u tri grupe na bazi homologije sekvenci, mehanizama prenosa signala, i farmakoloških svojstava. Grupa I obuhvata GRM1 i GRM5. Za njih je pokazano da aktiviraju [[fosfolipaza C|fosfolipazu C]]. Grupa II obuhvata GRM2 i GRM3, dok su grupi III GRM4, GRM6, GRM7 i GRM8. Grupe II i III receptora su povezane sa inhibicijom kaskade [[Ciklični adenozin monofosfat|cikličnog AMP-a]], ali se razlikuju u selektivnost na agoniste.<ref name="entrez"/>
}}

== Ligandi ==
Potpuno mGluR3 selektivni agensi nisu dostupni. Poznati su mešoviti mGluR2/3 (grupa II) ligandi sa selektivnošću u odnosu na druge mGluR podtipove. Neki od njih imaju nisku oralnu [[biodostupnost]], ali postoji mogućnost njihove upotrebe u obliku [[prolek]]a.<ref>{{cite journal |author=Rorick-Kehn LM, Perkins EJ, Knitowski KM, ''et al.'' |title=Improved bioavailability of the mGlu2/3 receptor agonist LY354740 using a prodrug strategy: in vivo pharmacology of LY544344 |journal=J. Pharmacol. Exp. Ther. |volume=316 |issue=2 |pages=905–13 |year=2006 |pmid=16223873 |doi=10.1124/jpet.105.091926 |url=https://archive.org/details/sim_journal-of-pharmacology-and-experimental-therapeutics_2006-02_316_2/page/905}}</ref>

=== Agonisti ===
* sa biciklo[3.1.0]heksanskom osnovom
** MGS-0028<ref>{{cite journal |author=Nakazato A, Kumagai T, Sakagami K, ''et al.'' |title=Synthesis, SARs, and pharmacological characterization of 2-amino-3 or 6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent, selective, and orally active group II metabotropic glutamate receptor agonists |journal=J. Med. Chem. |volume=43 |issue=25 |pages=4893–909 |year=2000 |pmid=11123999|doi=10.1021/jm000346k}}</ref>
** LY404040<ref>{{cite journal |author=Monn JA, Massey SM, Valli MJ, ''et al.'' |title=Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: identification of potent, selective, and orally bioavailable agonists for mGlu2/3 receptors |journal=J. Med. Chem. |volume=50 |issue=2 |pages=233–40 |year=2007 |pmid=17228865 |doi=10.1021/jm060917u |url=}}</ref>
** LY379268<ref>{{cite journal |author=Monn JA, Valli MJ, Massey SM, ''et al.'' |title=Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (LY354740): identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors |journal=J. Med. Chem. |volume=42 |issue=6 |pages=1027–40 |year=1999 |pmid=10090786 |doi=10.1021/jm980616n |url=}}</ref>
** [[Eglumegad|LY354740]]<ref>{{cite journal |author=Monn JA, Valli MJ, Massey SM, ''et al.'' |title=Design, synthesis, and pharmacological characterization of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740): a potent, selective, and orally active group 2 metabotropic glutamate receptor agonist possessing anticonvulsant and anxiolytic properties |journal=J. Med. Chem. |volume=40 |issue=4 |pages=528–37 |year=1997 |pmid=9046344 |doi=10.1021/jm9606756 |url=}}</ref>; njegov (+)-C4α-metil analog je GluR2 agonist / GluR3 antagonist<ref>{{cite journal |author=Dominguez C, Prieto L, Valli MJ, ''et al.'' |title=Methyl substitution of 2-aminobicyclo[3.1.0]hexane 2,6-dicarboxylate (LY354740) determines functional activity at metabotropic glutamate receptors: identification of a subtype selective mGlu2 receptor agonist |journal=J. Med. Chem. |volume=48 |issue=10 |pages=3605–12 |year=2005 |pmid=15887967 |doi=10.1021/jm040222y |url=}}</ref>
* (''R'')-2-amino-4-(4-hidroksi[1,2,5]tiadiazol-3-il)buterna kiselina<ref>{{cite journal |author=Clausen RP, Bräuner-Osborne H, Greenwood JR, ''et al.'' |title=Selective agonists at group II metabotropic glutamate receptors: synthesis, stereochemistry, and molecular pharmacology of (S)- and (R)-2-amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl)butyric acid |journal=J. Med. Chem. |volume=45 |issue=19 |pages=4240–5 |year=2002 |pmid=12213064|doi=10.1021/jm020122x}}</ref>

=== Antagonist ===
* [[CECXG]] - 38 puta je selektivniji za mGlu<sub>3</sub> u odnosu na mGlu<sub>2</sub>
* [[LY-341,495]] i njegov 1-fluoro analog<ref>{{cite journal |author=Sakagami K, Yasuhara A, Chaki S, ''et al.'' |title=Synthesis, in vitro pharmacology, and pharmacokinetic profiles of 2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid and its 6-heptyl ester, a potent mGluR2 antagonist |journal=Bioorg. Med. Chem. |volume=16 |issue=8 |pages=4359–66 |year=2008 |pmid=18348906 |doi=10.1016/j.bmc.2008.02.066 |url=}}</ref>: potentni ortosterni antagonisti
* [[MGS-0039]]<ref>a) {{cite journal |author=Nakazato A, Sakagami K, Yasuhara A, ''et al.'' |title=Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists |journal=J. Med. Chem. |volume=47 |issue=18 |pages=4570–87 |year=2004 |pmid=15317467 |doi=10.1021/jm0400294 |url=}}, <br />b) {{cite journal |author=Yasuhara A, Nakamura M, Sakagami K, ''et al.'' |title=Prodrugs of 3-(3,4-dichlorobenzyloxy)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039): a potent and orally active group II mGluR antagonist with antidepressant-like potential |journal=Bioorg. Med. Chem. |volume=14 |issue=12 |pages=4193–207 |year=2006 |pmid=16487713 |doi=10.1016/j.bmc.2006.01.060 |url=}}, <br />c) {{cite journal |author=Yasuhara A, Sakagami K, Yoshikawa R, Chaki S, Nakamura M, Nakazato A |title=Synthesis, in vitro pharmacology, and structure-activity relationships of 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as mGluR2 antagonists |journal=Bioorg. Med. Chem. |volume=14 |issue=10 |pages=3405–20 |year=2006 |pmid=16431115 |doi=10.1016/j.bmc.2005.12.061 |url=}}</ref>, [[HYDIA]]<ref>{{cite journal |author=Woltering TJ, Adam G, Huguenin P, ''et al.'' |title=Asymmetric synthesis and receptor pharmacology of the group II mGlu receptor ligand (1S,2R,3R,5R,6S)-2-amino-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid-HYDIA |journal=ChemMedChem |volume=3 |issue=2 |pages=323–35 |year=2008 |pmid=18058780 |doi=10.1002/cmdc.200700226 |url=}}</ref> (oba sa biciklo[3.1.0]heksanskom osnovom)

=== Alosterni modulatori ===
* MNI-137<ref>{{cite journal |author=Hemstapat K, Da Costa H, Nong Y, ''et al.'' |title=A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors |journal=J. Pharmacol. Exp. Ther. |volume=322 |issue=1 |pages=254–64 |year=2007 |pmid=17416742 |doi=10.1124/jpet.106.117093 |url=https://archive.org/details/sim_journal-of-pharmacology-and-experimental-therapeutics_2007-07_322_1/page/254}}</ref>: inhibitor
* jedinjenje 7p<ref>{{cite journal |author=Woltering TJ, Wichmann J, Goetschi E, ''et al.'' |title=Synthesis and characterization of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: Part 3. New potent non-competitive metabotropic glutamate receptor 2/3 antagonists |journal=Bioorg. Med. Chem. Lett. |volume=18 |issue=8 |pages=2725–9 |year=2008 |pmid=18374569 |doi=10.1016/j.bmcl.2008.02.076 |url=}}</ref>: nekompetitivni antagonist

== Interakcije ==
Metabotropni glutamatni receptor 3 formira [[Protein-protein interakcija|interakcije]] sa [[GRIP1 (gen)|GRIP1]],<ref name=pmid11891216>{{cite journal |last=Hirbec |first=Hélène |authorlink= |coauthors=Perestenko Olga, Nishimune Atsushi, Meyer Guido, Nakanishi Shigetada, Henley Jeremy M, Dev Kumlesh K |year= 2002 |month=May |title=The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs |journal=J. Biol. Chem. |volume=277 |issue=18 |pages=15221–4 |publisher= |location = United States| issn = 0021-9258| pmid = 11891216 |doi = 10.1074/jbc.C200112200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref> [[PICK1]]<ref name=pmid11891216/> i [[PPM1A]].<ref name=pmid14663150>{{cite journal |last=Flajolet |first=Marc |authorlink= |coauthors=Rakhilin Sergey, Wang Hong, Starkova Natalia, Nuangchamnong Nina, Nairn Angus C, Greengard Paul |year= 2003 |month=December |title=Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue=26 |pages=16006–11 |publisher= |location = United States| issn = 0027-8424| pmid = 14663150 |doi = 10.1073/pnas.2136600100 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |pmc=307683 }}</ref>

== Reference ==
{{Reflist|2}}

== Literatura ==
{{refbegin | 2}}
{{PBB_Further_reading 
| citations = 
*{{cite journal  | author=Makoff A, Volpe F, Lelchuk R, ''et al.'' |title=Molecular characterization and localization of human metabotropic glutamate receptor type 3. |journal=Brain Res. Mol. Brain Res. |volume=40 |issue= 1 |pages= 55–63 |year= 1997 |pmid= 8840013 |doi=10.1016/0169-328X(96)00037-X  }}
*{{cite journal  | author=Emile L, Mercken L, Apiou F, ''et al.'' |title=Molecular cloning, functional expression, pharmacological characterization and chromosomal localization of the human metabotropic glutamate receptor type 3. |journal=Neuropharmacology |volume=35 |issue= 5 |pages= 523–30 |year= 1997 |pmid= 8887960 |doi=10.1016/0028-3908(96)84622-3  }}
*{{cite journal  | author=Corti C, Sala CF, Yang F, ''et al.'' |title=Genomic organization of the human metabotropic glutamate receptor subtype 3. |journal=J. Neurogenet. |volume=14 |issue= 4 |pages= 207–25, 271 |year= 2001 |pmid= 11342382 |doi=10.3109/01677060009084499  }}
*{{cite journal  | author=Corti C, Xuereb JH, Corsi M, Ferraguti F |title=Identification and characterization of the promoter region of the GRM3 gene. |journal=Biochem. Biophys. Res. Commun. |volume=286 |issue= 2 |pages= 381–7 |year= 2001 |pmid= 11500049 |doi= 10.1006/bbrc.2001.5391 }}
*{{cite journal  | author=Tomiyama M, Kimura T, Maeda T, ''et al.'' |title=Expression of metabotropic glutamate receptor mRNAs in the human spinal cord: implications for selective vulnerability of spinal motor neurons in amyotrophic lateral sclerosis. |journal=J. Neurol. Sci. |volume=189 |issue= 1-2 |pages= 65–9 |year= 2001 |pmid= 11535235 |doi=10.1016/S0022-510X(01)00561-5  }}
*{{cite journal  | author=Rosemond E, Peltekova V, Naples M, ''et al.'' |title=Molecular determinants of high affinity binding to group III metabotropic glutamate receptors. |journal=J. Biol. Chem. |volume=277 |issue= 9 |pages= 7333–40 |year= 2002 |pmid= 11744707 |doi= 10.1074/jbc.M110476200 }}
*{{cite journal  | author=Martí SB, Cichon S, Propping P, Nöthen M |title=Metabotropic glutamate receptor 3 (GRM3) gene variation is not associated with schizophrenia or bipolar affective disorder in the German population. |journal=Am. J. Med. Genet. |volume=114 |issue= 1 |pages= 46–50 |year= 2002 |pmid= 11840505 |doi=10.1002/ajmg.1624  }}
*{{cite journal  | author=Kitano J, Kimura K, Yamazaki Y, ''et al.'' |title=Tamalin, a PDZ domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins. |journal=J. Neurosci. |volume=22 |issue= 4 |pages= 1280–9 |year= 2002 |pmid= 11850456 |doi=  }}
*{{cite journal  | author=Hirbec H, Perestenko O, Nishimune A, ''et al.'' |title=The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs. |journal=J. Biol. Chem. |volume=277 |issue= 18 |pages= 15221–4 |year= 2002 |pmid= 11891216 |doi= 10.1074/jbc.C200112200 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 }}
*{{cite journal  | author=Scherer SW, Cheung J, MacDonald JR, ''et al.'' |title=Human chromosome 7: DNA sequence and biology. |journal=Science |volume=300 |issue= 5620 |pages= 767–72 |year= 2003 |pmid= 12690205  | pmc=2882961 |doi= 10.1126/science.1083423 }}
*{{cite journal  | author=Fujii Y, Shibata H, Kikuta R, ''et al.'' |title=Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia. |journal=Psychiatr. Genet. |volume=13 |issue= 2 |pages= 71–6 |year= 2004 |pmid= 12782962 |doi= 10.1097/01.ypg.0000056682.82896.b0 }}
*{{cite journal  | author=Aronica E, Gorter JA, IJlst-Keizers H, ''et al.'' |title=Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. |journal=Eur. J. Neurosci. |volume=17 |issue= 10 |pages= 2106–18 |year= 2003 |pmid= 12786977 |doi=10.1046/j.1460-9568.2003.02657.x  }}
*{{cite journal  | author=Hillier LW, Fulton RS, Fulton LA, ''et al.'' |title=The DNA sequence of human chromosome 7. |journal=Nature |volume=424 |issue= 6945 |pages= 157–64 |year= 2003 |pmid= 12853948 |doi= 10.1038/nature01782 }}
*{{cite journal  | author=Flajolet M, Rakhilin S, Wang H, ''et al.'' |title=Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue= 26 |pages= 16006–11 |year= 2004 |pmid= 14663150 |doi= 10.1073/pnas.2136600100  | pmc=307683 }}
*{{cite journal  | author=Yao Y, Koo JC, Wells JW, Hampson DR |title=Expression of a truncated secreted form of the mGluR3 subtype of metabotropic glutamate receptor. |journal=Biochem. Biophys. Res. Commun. |volume=319 |issue= 2 |pages= 622–8 |year= 2004 |pmid= 15178451 |doi= 10.1016/j.bbrc.2004.05.032 }}
*{{cite journal  | author=Tang FR, Chia SC, Chen PM, ''et al.'' |title=Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus. |journal=Epilepsy Res. |volume=59 |issue= 2-3 |pages= 167–80 |year= 2004 |pmid= 15246118 |doi= 10.1016/j.eplepsyres.2004.04.002 }}
*{{cite journal  | author=Egan MF, Straub RE, Goldberg TE, ''et al.'' |title=Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 34 |pages= 12604–9 |year= 2004 |pmid= 15310849 |doi= 10.1073/pnas.0405077101  | pmc=515104 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 }}
}}
{{refend}}

== Povezano ==
* [[Metabotropni glutamatni receptor]]

== Vanjske veze ==
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2272 | title = Metabotropic Glutamate Receptors: mGlu<sub>3</sub> | accessdate =  | author =  | authorlink =  | coauthors =  | date =  | format =  | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages =  | language =  | archiveurl = https://web.archive.org/web/20140808050638/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2272 | archivedate = 2014-08-08 | quote =  | dead-url = yes }}
{{-}}
{{PDB Galerija-lat|geneid=2913}}
{{G protein spregnuti receptori-lat}}
{{Glutamatergični ligandi-lat}}

[[Kategorija:G protein spregnuti receptori]]