Oksitocinski receptor
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| Oksitocinski receptor | |||||||||||
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| Identifikatori | |||||||||||
| Simboli | OXTR; OT-R | ||||||||||
| Vanjski ID | OMIM: 167055 MGI: 109147 HomoloGene: 20255 IUPHAR: OT GeneCards: OXTR Gene | ||||||||||
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| Pregled RNK izražavanja | |||||||||||
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| Ortolozi | |||||||||||
| Vrsta | Čovek | Miš | |||||||||
| Entrez | 5021 | 18430 | |||||||||
| Ensembl | ENSG00000180914 | ENSMUSG00000049112 | |||||||||
| UniProt | P30559 | Q3UPP9 | |||||||||
| RefSeq (mRNA) | NM_000916 | XM_001001627 | |||||||||
| RefSeq (protein) | NP_000907 | XP_001001627 | |||||||||
| Lokacija (UCSC) | Chr 3: 8.77 - 8.79 Mb | Chr 6: 112.44 - 112.46 Mb | |||||||||
| PubMed pretraga | [1] | [2] | |||||||||
Oksitocinski receptor, ili OXTR, je protein koji dejstvuje kao receptor za hormon i neurotransmiter oksitocin.[1][2] Kod ljudi, oksitocinski receptor je kodiran OXTR genom.[3][4], koji je lokalizovan na ljudskom hromozomu 3p25.[5]
Funkcija i lokacija
OXTR protein pripada familiji G-protein spregnutih receptora, specifično Gq,[1] i dejstvuje kao receptor za oksitocin. Njegova aktivnost je posredovana G proteinima koji aktiviraju više različitih sistema sekundarnih glasnika.[6][7]
Oksitocinski receptori su izraženi u mioepitelijalnim ćelijama mlečnih žlezdi, i u miometrijumu i endometrijumu uterusa na kraju trudnoće. Sistem oksitocina ima važnu ulogu indukovanja uterinskih kontrakcija tokom porođaja i izbacivanja mleka.
Oksitocinski receptori su takođe prisutni u centralnom nervnom sistemu. Ti receptori modulišu više odlika ponašanja, poput stresa i anksioznosti, socijalne memorije i prepoznavanja, seksualnog i agresivnog ponašanja, druženja (afilijacije) i materinskog ponašanja.[8][9][10]
Ko nekih sisara, oksitocinski receptori su takođe nađeni u bubrezima i srcu.
Ligandi
Nekoliko selektivnih liganda oksitocinskih receptora je nedavno bilo razvijeno, ali značajna sličnost između oksitocinskog i srodnog vazopresinskog receptora onemogućava visoku selektivnost.[11][12]
Agonisti
- Peptidi
- Non-peptidni
- Jedinjenje 39 (Ki = 33 nM, 25x selektivan u odnosu na vazopresin receptore)[13]
Jedinjenje 39 - WAY-267,464 – anksiolitik kod miševa[12][14][15]
Antagonisti
- Peptid
- Non-peptidni
- GSK-221,149
- L-368,899 (CAS# 148927-60-0)[16][17]
- L-371,257 (CAS# 162042-44-6)[18][19] – periferno selektivan (npr. slaba penetracija moždano-krvne barijere, malo centralnih efekata)[20]
- L-372,662
- SSR-126,768
- WAY-162,720 – centralno antagonist aktivan nakon periferne administracije
Reference
- ↑ 1,0 1,1 Gimpl G, Fahrenholz F (2001). „The oxytocin receptor system: structure, function, and regulation”. Physiological Reviews 81 (2): 629–83. PMID 11274341. Arhivirano iz originala na datum 2009-04-02. Pristupljeno 2014-04-17.
- ↑ Zingg HH, Laporte SA (2003). „The oxytocin receptor”. Trends in Endocrinology and Metabolism 14 (5): 222–7. DOI:10.1016/S1043-2760(03)00080-8. PMID 12826328.
- ↑ „Entrez Gene: OXTR oxytocin receptor”.
- ↑ Kimura T, Tanizawa O, Mori K, Brownstein MJ, Okayama H (April 1992). „Structure and expression of a human oxytocin receptor”. Nature 356 (6369): 526–9. DOI:10.1038/356526a0. PMID 1313946.
- ↑ Simmons CF Jr, Clancy TE, Quan R, Knoll JH (1965). „The oxytocin receptor gene (OXTR) localizes to human chromosome 3p25 by fluorescence in situ hybridization and PCR analysis of somatic cell hybrids”. Genomics 26 (3): 623–5. DOI:10.1016/0888-7543(95)80188-R. ISSN 0888-7543. PMID 7607693.
- ↑ Devost D, Wrzal P, Zingg HH. Oxytocin receptor signalling. Progress in Brain Research. 2008;170:167-76. PMID 18655881
- ↑ Gimpl G, Reitz J, Brauer S, Trossen C. Oxytocin receptors: ligand binding, signalling and cholesterol dependence. Progress in Brain Research. 2008;170:193-204. PMID 18655883
- ↑ Caldwell HK, Young WS 3rd (2006). „Oxytocin and Vasopressin: Genetics and Behavioral Implications”. u: Lajtha, Abel; Ramon Lim. Handbook of Neurochemistry and Molecular Neurobiology (3rd izd.). Berlin: Springer. str. 573–607. ISBN 0-387-30348-0.
- ↑ Kiss A, Mikkelsen JD (September 2005). „Oxytocin--anatomy and functional assignments: a minireview”. Endocrine Regulations 39 (3): 97–105. PMID 16468232.
- ↑ Veenema AH, Neumann ID (2008). „Central vasopressin and oxytocin release: regulation of complex social behaviours”. Progress in Brain Research 170: 261–76. DOI:10.1016/S0079-6123(08)00422-6. PMID 18655888.
- ↑ Chini B, Manning M (August 2007). „Agonist selectivity in the oxytocin/vasopressin receptor family: new insights and challenges”. Biochemical Society Transactions 35 (Pt 4): 737–41. DOI:10.1042/BST0350737. PMID 17635137.
- ↑ 12,0 12,1 Manning M, Stoev S, Chini B, Durroux T, Mouillac B, Guillon G (2008). „Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents”. Progress in Brain Research 170: 473–512. DOI:10.1016/S0079-6123(08)00437-8. PMID 18655903.
- ↑ Pitt GR, Batt AR, Haigh RM, Penson AM, Robson PA, Rooker DP, Tartar AL, Trim JE, Yea CM, Roe MB (September 2004). „Non-peptide oxytocin agonists”. Bioorganic & Medicinal Chemistry Letters 14 (17): 4585–9. DOI:10.1016/j.bmcl.2004.04.107. PMID 15357997.
- ↑ Rahman Z, Resnick L, Rosenzweig-Lipson SJ, Ring RH,"Methods of treatment using oxytocin receptor agonists", US patent application 2007/0117794, published 24. 5. 2007. , assigned to Wyeth Corp
- ↑ Ring RH, Schechter LE, Leonard SK, Dwyer JM, Platt BJ, Graf R, Grauer S, Pulicicchio C, Resnick L, Rahman Z, Sukoff Rizzo SJ, Luo B, Beyer CE, Logue SF, Marquis KL, Hughes ZA, Rosenzweig-Lipson S (July 2009). „Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin receptor agonist”. Neuropharmacology 58 (1): 69–77. DOI:10.1016/j.neuropharm.2009.07.016. PMID 19615387.
- ↑ Williams PD, Anderson PS, Ball RG, Bock MG, Carroll L, Chiu SH, Clineschmidt BV, Culberson JC, Erb JM, Evans BE (March 1994). „1-((7,7-Dimethyl-2(S)-(2(S)-amino-4-(methylsulfonyl)butyramido)bicyclo [2.2.1]-heptan-1(S)-yl)methyl)sulfonyl)-4-(2-methylphenyl)piperaz ine (L-368,899): an orally bioavailable, non-peptide oxytocin antagonist with potential utility for managing preterm labor”. Journal of Medicinal Chemistry 37 (5): 565–71. DOI:10.1021/jm00031a004. PMID 8126695.
- ↑ Boccia ML, Goursaud AP, Bachevalier J, Anderson KD, Pedersen CA (September 2007). „Peripherally administered non-peptide oxytocin antagonist, L368,899, accumulates in limbic brain areas: a new pharmacological tool for the study of social motivation in non-human primates”. Hormones and Behavior 52 (3): 344–51. DOI:10.1016/j.yhbeh.2007.05.009. PMC 2712625. PMID 17583705.
- ↑ Williams PD, Clineschmidt BV, Erb JM, Freidinger RM, Guidotti MT, Lis EV, Pawluczyk JM, Pettibone DJ, Reiss DR, Veber DF (November 1995). „1-(1-[4-[(N-acetyl-4-piperidinyl)oxy]-2-methoxybenzoyl]piperidin-4- yl)-4H-3,1-benzoxazin-2(1H)-one (L-371,257): a new, orally bioavailable, non-peptide oxytocin antagonist”. Journal of Medicinal Chemistry 38 (23): 4634–6. DOI:10.1021/jm00023a002. PMID 7473590.
- ↑ Wyatt PG, Allen MJ, Chilcott J, Foster A, Livermore DG, Mordaunt JE, Scicinski J, Woollard PM (May 2002). „Identification of potent and selective oxytocin antagonists. Part 1: indole and benzofuran derivatives”. Bioorganic & Medicinal Chemistry Letters 12 (10): 1399–404. DOI:10.1016/S0960-894X(02)00159-2. PMID 11992786.
- ↑ Ring RH, Malberg JE, Potestio L, Ping J, Boikess S, Luo B, Schechter LE, Rizzo S, Rahman Z, Rosenzweig-Lipson S (April 2006). „Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications”. Psychopharmacology (Berlin) 185 (2): 218–25. DOI:10.1007/s00213-005-0293-z. PMID 16418825.
Literatura
- „Symbol Report: OXTR”. Human Geneome Organization Gene Nomenclature Committee. Arhivirano iz originala na datum 2010-06-18. Pristupljeno 2014-04-17.
- „Vasopressin and Oxytocin Receptors: OT”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-03.
- Caldwell HK, Young WS 3rd (2006). „Oxytocin and Vasopressin: Genetics and Behavioral Implications”. u: Lajtha, Abel; Ramon Lim. Handbook of Neurochemistry and Molecular Neurobiology (3rd izd.). Berlin: Springer. str. 573–607.
Spoljašnje veze
- MeSH Oxytocin+receptor
- p
- r
- u
Drugi | Moždano specifični angiogenezni inhibitor (1, 2, 3) • Cadherin (1, 2, 3) • Kalcitonin • CALCRL • CD97 • Kortikotropin-oslobađajući hormon (1, 2) • EMR (1, 2, 3) • Glukagon (GR, GIPR, GLP1R, GLP2R) • Hormon rasta oslobađajući hormon • PACAPR1 • GPR • Latrofilin (1, 2, 3, ELTD1) • Metuselah-slični proteini • Paratiroidni hormon (1, 2) • Sekretin • Vazoaktivni intestinalni peptid (1, 2) |
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glutamat / feromon
Drugi |
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Frizzled / Zaglađeni
Uvojiti | |
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Zaglađeni |
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
