Oksitocinski receptor

Oksitocinski receptor
Oksitocinski receptor
Identifikatori
Simboli	OXTR; OT-R
Vanjski ID	OMIM: 167055 MGI: 109147 HomoloGene: 20255 IUPHAR: OT GeneCards: OXTR Gene
Ontologija gena
Molekularna funkcija	• rodopsinu-slična receptorska aktivnost; • receptorska aktivnost; • receptorska aktivnost oksitocina; • receptorska aktivnost vazopresina;
Celularna komponenta	• endosom; • membrana plazme; • integralno sa membranom plazme;
Biološki proces	• kontrakcija mišića; • G-protein signalizacija, spregnuta sa IP3 sekundarnim glasnikom (aktivacija fosfolipaze C); • trudnoća; • laktacija;
Pregled RNK izražavanja
	podaci
Ortolozi
Vrsta	Čovek
Entrez	5021
Ensembl	ENSG00000180914
UniProt	P30559
RefSeq (mRNA)	NM_000916
RefSeq (protein)	NP_000907
Lokacija (UCSC)	Chr 3:; 8.77 - 8.79 Mb
PubMed pretraga	[1]

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 G_q,^[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 (K_i = 33 nM, 25x selektivan u odnosu na vazopresin receptore)^[13]

Jedinjenje 39
WAY-267,464 – anksiolitik kod miševa^[12]^[14]^[15]

Antagonisti

Peptid

Atosiban

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

^ ^а ^б Gimpl G, Fahrenholz F (2001). „The oxytocin receptor system: structure, function, and regulation”. Physiological Reviews. 81 (2): 629—83. PMID 11274341. doi:10.1152/physrev.2001.81.2.629. Архивирано из оригинала 02. 04. 2009. г. Приступљено 11. 10. 2010.
^ Zingg HH, Laporte SA (2003). „The oxytocin receptor”. Trends in Endocrinology and Metabolism. 14 (5): 222—7. PMID 12826328. S2CID 21540056. doi:10.1016/S1043-2760(03)00080-8.
^ „Entrez Gene: OXTR oxytocin receptor”.
^ Kimura T, Tanizawa O, Mori K, Brownstein MJ, Okayama H (1992). „Structure and expression of a human oxytocin receptor”. Nature. 356 (6369): 526—9. PMID 1313946. S2CID 4273722. doi:10.1038/356526a0.
^ Simmons CF Jr; Clancy, TE; Quan R; Knoll, JH (1995). „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. ISSN 0888-7543. PMID 7607693. doi:10.1016/0888-7543(95)80188-R.
^ Devost, D.; Wrzal, P.; Zingg, H. H. (2008). „Oxytocin receptor signalling”. Advances in Vasopressin and Oxytocin — from Genes to Behaviour to Disease. Progress in Brain Research. 170. стр. 167—76. ISBN 9780444532015. PMID 18655881. doi:10.1016/S0079-6123(08)00415-9.
^ Gimpl, G.; Reitz, J.; Brauer, S.; Trossen, C. (2008). „Oxytocin receptors: Ligand binding, signalling and cholesterol dependence”. Advances in Vasopressin and Oxytocin — from Genes to Behaviour to Disease. Progress in Brain Research. 170. стр. 193—204. ISBN 9780444532015. PMID 18655883. doi:10.1016/S0079-6123(08)00417-2.
^ Caldwell HK, Young WS 3rd (2006). „Oxytocin and Vasopressin: Genetics and Behavioral Implications”. Ур.: Lajtha, Abel; Ramon Lim. Handbook of Neurochemistry and Molecular Neurobiology (3rd изд.). Berlin: Springer. стр. 573–607. ISBN 978-0-387-30348-2.
^ Kiss A, Mikkelsen JD (2005). „Oxytocin--anatomy and functional assignments: a minireview” (PDF). Endocrine Regulations. 39 (3): 97—105. PMID 16468232.
^ Veenema AH, Neumann ID (2008). „Central vasopressin and oxytocin release: regulation of complex social behaviours”. Advances in Vasopressin and Oxytocin — from Genes to Behaviour to Disease. Progress in Brain Research. 170. стр. 261—76. ISBN 9780444532015. PMID 18655888. doi:10.1016/S0079-6123(08)00422-6.
^ Chini B, Manning M (2007). „Agonist selectivity in the oxytocin/vasopressin receptor family: new insights and challenges”. Biochemical Society Transactions. 35 (Pt 4): 737—41. PMID 17635137. doi:10.1042/BST0350737.
^ ^а ^б 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. стр. 473—512. PMID 18655903. doi:10.1016/S0079-6123(08)00437-8.
^ Pitt GR, Batt AR, Haigh RM, Penson AM, Robson PA, Rooker DP, Tartar AL, Trim JE, Yea CM, Roe MB (2004). „Non-peptide oxytocin agonists”. Bioorganic & Medicinal Chemistry Letters. 14 (17): 4585—9. PMID 15357997. doi:10.1016/j.bmcl.2004.04.107.
^ 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 (2009). „Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin receptor agonist”. Neuropharmacology. 58 (1): 69—77. PMID 19615387. S2CID 8592340. doi:10.1016/j.neuropharm.2009.07.016.
^ Williams PD, Anderson PS, Ball RG, Bock MG, Carroll L, Chiu SH, Clineschmidt BV, Culberson JC, Erb JM, Evans BE (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. PMID 8126695. doi:10.1021/jm00031a004.
^ Boccia ML, Goursaud AP, Bachevalier J, Anderson KD, Pedersen CA (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. PMC 2712625  . PMID 17583705. doi:10.1016/j.yhbeh.2007.05.009.
^ Williams PD, Clineschmidt BV, Erb JM, Freidinger RM, Guidotti MT, Lis EV, Pawluczyk JM, Pettibone DJ, Reiss DR, Veber DF (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. PMID 7473590. doi:10.1021/jm00023a002.
^ Wyatt PG, Allen MJ, Chilcott J, Foster A, Livermore DG, Mordaunt JE, Scicinski J, Woollard PM (2002). „Identification of potent and selective oxytocin antagonists. Part 1: indole and benzofuran derivatives”. Bioorganic & Medicinal Chemistry Letters. 12 (10): 1399—404. PMID 11992786. doi:10.1016/S0960-894X(02)00159-2.
^ Ring RH, Malberg JE, Potestio L, Ping J, Boikess S, Luo B, Schechter LE, Rizzo S, Rahman Z, Rosenzweig-Lipson S (2006). „Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications”. Psychopharmacology (Berlin). 185 (2): 218—25. PMID 16418825. S2CID 13647805. doi:10.1007/s00213-005-0293-z.

Dodatna literatura

„Symbol Report: OXTR”. Human Geneome Organization Gene Nomenclature Committee. Архивирано из оригинала 18. 06. 2010. г. Приступљено 11. 10. 2010.
„Vasopressin and Oxytocin Receptors: OT”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 03. 03. 2016. г.
Caldwell HK, Young WS 3rd (2006). „Oxytocin and Vasopressin: Genetics and Behavioral Implications”. Ур.: Lajtha, Abel; Ramon Lim. Handbook of Neurochemistry and Molecular Neurobiology (3rd изд.). Berlin: Springer. стр. 573—607.

Spoljašnje veze

Oxytocin+receptor на US National Library of Medicine Medical Subject Headings (MeSH)

[pmid11274341-1] а ^б Gimpl G, Fahrenholz F (2001). „The oxytocin receptor system: structure, function, and regulation”. Physiological Reviews. 81 (2): 629—83. PMID 11274341. doi:10.1152/physrev.2001.81.2.629. Архивирано из оригинала 02. 04. 2009. г. Приступљено 11. 10. 2010.

[pmid12826328-2] Zingg HH, Laporte SA (2003). „The oxytocin receptor”. Trends in Endocrinology and Metabolism. 14 (5): 222—7. PMID 12826328. S2CID 21540056. doi:10.1016/S1043-2760(03)00080-8.

[entrez-3] „Entrez Gene: OXTR oxytocin receptor”.

[pmid1313946-4] Kimura T, Tanizawa O, Mori K, Brownstein MJ, Okayama H (1992). „Structure and expression of a human oxytocin receptor”. Nature. 356 (6369): 526—9. PMID 1313946. S2CID 4273722. doi:10.1038/356526a0.

[pmid7607693-5] Simmons CF Jr; Clancy, TE; Quan R; Knoll, JH (1995). „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. ISSN 0888-7543. PMID 7607693. doi:10.1016/0888-7543(95)80188-R.

[6] Devost, D.; Wrzal, P.; Zingg, H. H. (2008). „Oxytocin receptor signalling”. Advances in Vasopressin and Oxytocin — from Genes to Behaviour to Disease. Progress in Brain Research. 170. стр. 167—76. ISBN 9780444532015. PMID 18655881. doi:10.1016/S0079-6123(08)00415-9.

[7] Gimpl, G.; Reitz, J.; Brauer, S.; Trossen, C. (2008). „Oxytocin receptors: Ligand binding, signalling and cholesterol dependence”. Advances in Vasopressin and Oxytocin — from Genes to Behaviour to Disease. Progress in Brain Research. 170. стр. 193—204. ISBN 9780444532015. PMID 18655883. doi:10.1016/S0079-6123(08)00417-2.

[isbn0-387-30348-0-8] Caldwell HK, Young WS 3rd (2006). „Oxytocin and Vasopressin: Genetics and Behavioral Implications”. Ур.: Lajtha, Abel; Ramon Lim. Handbook of Neurochemistry and Molecular Neurobiology (3rd изд.). Berlin: Springer. стр. 573–607. ISBN 978-0-387-30348-2.

[pmid16468232-9] Kiss A, Mikkelsen JD (2005). „Oxytocin--anatomy and functional assignments: a minireview” (PDF). Endocrine Regulations. 39 (3): 97—105. PMID 16468232.

[pmid18655888-10] Veenema AH, Neumann ID (2008). „Central vasopressin and oxytocin release: regulation of complex social behaviours”. Advances in Vasopressin and Oxytocin — from Genes to Behaviour to Disease. Progress in Brain Research. 170. стр. 261—76. ISBN 9780444532015. PMID 18655888. doi:10.1016/S0079-6123(08)00422-6.

[pmid17635137-11] Chini B, Manning M (2007). „Agonist selectivity in the oxytocin/vasopressin receptor family: new insights and challenges”. Biochemical Society Transactions. 35 (Pt 4): 737—41. PMID 17635137. doi:10.1042/BST0350737.

[pmid18655903-12] а ^б 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. стр. 473—512. PMID 18655903. doi:10.1016/S0079-6123(08)00437-8.

[pmid15357997-13] Pitt GR, Batt AR, Haigh RM, Penson AM, Robson PA, Rooker DP, Tartar AL, Trim JE, Yea CM, Roe MB (2004). „Non-peptide oxytocin agonists”. Bioorganic & Medicinal Chemistry Letters. 14 (17): 4585—9. PMID 15357997. doi:10.1016/j.bmcl.2004.04.107.

[WO_2007050353-14] 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

[pmid19615387-15] 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 (2009). „Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin receptor agonist”. Neuropharmacology. 58 (1): 69—77. PMID 19615387. S2CID 8592340. doi:10.1016/j.neuropharm.2009.07.016.

[pmid8126695-16] Williams PD, Anderson PS, Ball RG, Bock MG, Carroll L, Chiu SH, Clineschmidt BV, Culberson JC, Erb JM, Evans BE (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. PMID 8126695. doi:10.1021/jm00031a004.

[pmid17583705-17] Boccia ML, Goursaud AP, Bachevalier J, Anderson KD, Pedersen CA (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. PMC 2712625  . PMID 17583705. doi:10.1016/j.yhbeh.2007.05.009.

[pmid7473590-18] Williams PD, Clineschmidt BV, Erb JM, Freidinger RM, Guidotti MT, Lis EV, Pawluczyk JM, Pettibone DJ, Reiss DR, Veber DF (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. PMID 7473590. doi:10.1021/jm00023a002.

[pmid11992786-19] Wyatt PG, Allen MJ, Chilcott J, Foster A, Livermore DG, Mordaunt JE, Scicinski J, Woollard PM (2002). „Identification of potent and selective oxytocin antagonists. Part 1: indole and benzofuran derivatives”. Bioorganic & Medicinal Chemistry Letters. 12 (10): 1399—404. PMID 11992786. doi:10.1016/S0960-894X(02)00159-2.

[pmid16418825-20] Ring RH, Malberg JE, Potestio L, Ping J, Boikess S, Luo B, Schechter LE, Rizzo S, Rahman Z, Rosenzweig-Lipson S (2006). „Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications”. Psychopharmacology (Berlin). 185 (2): 218—25. PMID 16418825. S2CID 13647805. doi:10.1007/s00213-005-0293-z.

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