Beta-3 adrenergički receptor

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Beta-3 adrenergički receptor
Identifikatori
SimboliADRB3; BETA3AR
Vanjski IDOMIM: 109691 MGI: 87939 HomoloGene: 37250 IUPHAR: β3-adrenoceptor GeneCards: ADRB3 Gene
Ontologija gena
Molekularna funkcija • rodopsinu-slična receptorska aktivnost
• receptorska aktivnost
• beta3-adrenergička receptorska aktivnost
• beta-3 adrenergičko receptorsko vezivanje
• proteinska homodimerizaciona aktivnost
• norepinefrinsko vezivanje
Celularna komponenta • membranska frakcija
• ćelijska membrana
• integralno sa ćelijskom membranom
• receptorski kompleks
Biološki proces • ishranom indukovana termogeneza
• norepinefrin-epinefrinska vazodilacija tokom regulacije krvnog pritiska
• arestinom posredovana desenzitizacija signalnog puta G-protein spregnutog receptora
• ugljeno hidratni metabolički proces
• generacija prekursornih metabolita i energije
• metabolički proces energetske rezerve
• receptorom-posredovana endocitoza
• prenos signala
• aktivacija adenilat ciklaze
• response na hladnoću
• generacija toplote
• negativna regulacija veličine tela
• pozitivna regulacija MAPKKK kaskade
• diferencijacija smeđih masnih ćelija
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez15511556
EnsemblENSG00000188778ENSMUSG00000031489
UniProtP13945Q3UP63
RefSeq (mRNA)NM_000025NM_013462
RefSeq (protein)NP_000016NP_038490
Lokacija (UCSC)Chr 8:
37.94 - 37.94 Mb		Chr 8:
28.69 - 28.7 Mb
PubMed pretraga[1][2]

Beta-3 adrenergički receptor (β3 adrenoreceptor), takođe poznat kao ADRB3, je beta-adrenergički receptor. ADRB3 je takođe oznaka za ljudski gen koji ga kodira.[1]

Funkcija

Dejstva β3 receptora obuhvataju:

Ova receptor je lociran uglavnom u adipoznom tkivu i učestvuje u regulaciji lipolize i termogeneze. Za neki β3 agoniste je utvrđeno da imaju antistresno dejstvo u studijama na životinjama. To sugestira da ovaj receptor takođe ima ulogu u CNS. Beta3-receptori su nađeni u žučnoj kesi, mokraćnoj bešiki, i u moždanom adipoznom tkivu. Njihova uloga u fiziologiji žučne kese je nepoznata, mada se smatra da učestvuju u lipolizi i termogenezi u smeđoj masnoći. Smatra se da u mokraćnoj bešiki izazivaju relaksaciju bešike i sprečavaju mokrenje.[4]

Mehanizam akcije

Beta adrenergički receptori učestvuju u epinefrinom i norepinefrinom indukovanoj aktivaciji adenilat ciklaze putem aktivacije G proteina Gs tipa.[5]

Agonisti

  • L-796,568[9]
  • CL-316,243[10]
  • LY-368,842
  • Ro40-2148

Selektivni β3 agonisti mogu potencijalno da pospeše umanjenje telesne težine putem modulacije lipolize.[2]

Antagonisti

  • Za SR 59230A se mislilo da je selektivni β3 antagonist[11] ali je naknadno utvrđeno da je takođe antagonist α1 receptora.[12]

Interakcije

Za beta-3 adrenergički receptor je pokazano da interaguje sa Src.[13]

Reference

  1. ↑ „Entrez Gene: ADRB1 adrenergic, beta-1-, receptor”. 
  2. ↑ 2,0 2,1 Ferrer-Lorente R, Cabot C, Fernández-López JA, Alemany M (September 2005). „Combined effects of oleoyl-estrone and a β3-adrenergic agonist (CL316,243) on lipid stores of diet-induced overweight male Wistar rats”. Life Sciences 77 (16): 2051–8. DOI:10.1016/j.lfs.2005.04.008. PMID 15935402. 
  3. ↑ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.  Page 163
  4. ↑ Masaaki Sawa, Hiroshi Harada (2006). „Recent Developments in the Design of Orally Bioavailable β3-Adrenergic Receptor Agonists”. Current Medicinal Chemistry 13 (1): 25–37. DOI:10.2174/092986706775198006. PMID 16457637. 
  5. ↑ „Entrez Gene: ADRB3 adrenergic, beta-3-, receptor”. 
  6. ↑ Consoli D, Leggio GM, Mazzola C, Micale V, Drago F (November 2007). „Behavioral effects of the β3 adrenoceptor agonist SR58611A: is it the putative prototype of a new class of antidepressant/anxiolytic drugs?”. European Journal of Pharmacology 573 (1-3): 139–47. DOI:10.1016/j.ejphar.2007.06.048. PMID 17669397. 
  7. ↑ Overstreet DH, Stemmelin J, Griebel G (June 2008). „Confirmation of antidepressant potential of the selective β3 adrenoceptor agonist amibegron in an animal model of depression”. Pharmacology, Biochemistry, and Behavior 89 (4): 623–6. DOI:10.1016/j.pbb.2008.02.020. PMID 18358519. 
  8. ↑ Hicks A, McCafferty GP, Riedel E, Aiyar N, Pullen M, Evans C, Luce TD, Coatney RW, Rivera GC, Westfall TD, Hieble JP (October 2007). „GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog”. The Journal of Pharmacology and Experimental Therapeutics 323 (1): 202–9. DOI:10.1124/jpet.107.125757. PMID 17626794. 
  9. ↑ Larsen TM, Toubro S, van Baak MA, Gottesdiener KM, Larson P, Saris WH, Astrup A (2002). „Effect of a 28-d treatment with L-796568, a novel β3-adrenergic receptor agonist, on energy expenditure and body composition in obese men”. The American Journal of Clinical Nutrition 76 (4): 780–8. PMID 12324291. 
  10. ↑ Fu, L; Isobe, K; Zeng, Q; Suzukawa, K; Takekoshi, K; Kawakami, Y (2008). „The effects of beta(3)-adrenoceptor agonist CL-316,243 on adiponectin, adiponectin receptors and tumor necrosis factor-alpha expressions in adipose tissues of obese diabetic KKAy mice.”. European journal of pharmacology 584 (1): 202–6. DOI:10.1016/j.ejphar.2008.01.028. PMID 18304529. 
  11. ↑ Nisoli E, Tonello C, Landi M, Carruba MO (1996). „Functional studies of the first selective β3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes”. Mol. Pharmacol. 49 (1): 7–14. PMID 8569714. 
  12. ↑ Bexis S, Docherty JR (April 2009). „Role of alpha(1)- and β3-adrenoceptors in the modulation by SR59230A of the effects of MDMA on body temperature in the mouse”. British Journal of Pharmacology 158 (1): 259–66. DOI:10.1111/j.1476-5381.2009.00186.x. PMC 2795232. PMID 19422394. 
  13. ↑ Cao, W; Luttrell L M, Medvedev A V, Pierce K L, Daniel K W, Dixon T M, Lefkowitz R J, Collins S (December 2000). „Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation”. J. Biol. Chem. (UNITED STATES) 275 (49): 38131–4. DOI:10.1074/jbc.C000592200. ISSN 0021-9258. PMID 11013230. 

Literatura

  • Granneman JG, Lahners KN, Rao DD (1993). „Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block.”. Mol. Pharmacol. 42 (6): 964–70. PMID 1336117. 
  • Nahmias C, Blin N, Elalouf JM, et al. (1991). „Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes.”. EMBO J. 10 (12): 3721–7. PMC 453106. PMID 1718744. 
  • Emorine LJ, Marullo S, Briend-Sutren MM, et al. (1989). „Molecular characterization of the human beta 3-adrenergic receptor.”. Science 245 (4922): 1118–21. DOI:10.1126/science.2570461. PMID 2570461. 
  • Guan XM, Amend A, Strader CD (1995). „Determination of structural domains for G protein coupling and ligand binding in beta 3-adrenergic receptor.”. Mol. Pharmacol. 48 (3): 492–8. PMID 7565630. 
  • Rodriguez M, Carillon C, Coquerel A, et al. (1995). „Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain.”. Brain Res. Mol. Brain Res. 29 (2): 369–75. DOI:10.1016/0169-328X(94)00274-I. PMID 7609625. 
  • Clément K, Vaisse C, Manning BS, et al. (1995). „Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity.”. N. Engl. J. Med. 333 (6): 352–4. DOI:10.1056/NEJM199508103330605. PMID 7609752. 
  • Dib A, Adélaïde J, Chaffanet M, et al. (1995). „Characterization of the region of the short arm of chromosome 8 amplified in breast carcinoma.”. Oncogene 10 (5): 995–1001. PMID 7898940. 
  • Mahmoudian M (1994). „The complex of human Gs protein with the beta 3 adrenergic receptor: a computer-aided molecular modeling study.”. Journal of molecular graphics 12 (1): 22–8, 34. DOI:10.1016/0263-7855(94)80004-9. PMID 8011597. 
  • Wilkie TM, Chen Y, Gilbert DJ, et al. (1994). „Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors.”. Genomics 18 (2): 175–84. DOI:10.1006/geno.1993.1452. PMID 8288218. 
  • Krief S, Lönnqvist F, Raimbault S, et al. (1993). „Tissue distribution of beta 3-adrenergic receptor mRNA in man.”. J. Clin. Invest. 91 (1): 344–9. DOI:10.1172/JCI116191. PMC 330032. PMID 8380813. 
  • van Spronsen A, Nahmias C, Krief S, et al. (1993). „The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes.”. Eur. J. Biochem. 213 (3): 1117–24. DOI:10.1111/j.1432-1033.1993.tb17861.x. PMID 8389293. 
  • Lelias JM, Kaghad M, Rodriguez M, et al. (1993). „Molecular cloning of a human beta 3-adrenergic receptor cDNA.”. FEBS Lett. 324 (2): 127–30. DOI:10.1016/0014-5793(93)81377-C. PMID 8389717. 
  • Candelore MR, Deng L, Tota LM, et al. (1996). „Pharmacological characterization of a recently described human beta 3-adrenergic receptor mutant.”. Endocrinology 137 (6): 2638–41. DOI:10.1210/en.137.6.2638. PMID 8641219. 
  • Fujisawa T, Ikegami H, Yamato E, et al. (1996). „Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain.”. Diabetologia 39 (3): 349–52. DOI:10.1007/BF00418352. PMID 8721782. 
  • Higashi K, Ishikawa T, Ito T, et al. (1997). „Association of a genetic variation in the beta 3-adrenergic receptor gene with coronary heart disease among Japanese.”. Biochem. Biophys. Res. Commun. 232 (3): 728–30. DOI:10.1006/bbrc.1997.6339. PMID 9126344. 
  • Hoffstedt J, Poirier O, Thörne A, et al. (1999). „Polymorphism of the human beta3-adrenoceptor gene forms a well-conserved haplotype that is associated with moderate obesity and altered receptor function.”. Diabetes 48 (1): 203–5. DOI:10.2337/diabetes.48.1.203. PMID 9892244. 
  • Halushka MK, Fan JB, Bentley K, et al. (1999). „Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.”. Nat. Genet. 22 (3): 239–47. DOI:10.1038/10297. PMID 10391210. 
  • Kimura K, Sasaki N, Asano A, et al. (2000). „Mutated human beta3-adrenergic receptor (Trp64Arg) lowers the response to beta3-adrenergic agonists in transfected 3T3-L1 preadipocytes.”. Horm. Metab. Res. 32 (3): 91–6. DOI:10.1055/s-2007-978597. PMID 10786926. 
  • Cao W, Luttrell LM, Medvedev AV, et al. (2001). „Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation.”. J. Biol. Chem. 275 (49): 38131–4. DOI:10.1074/jbc.C000592200. PMID 11013230. 
  • Russell ST, Hirai K, Tisdale MJ (2002). „Role of beta3-adrenergic receptors in the action of a tumour lipid mobilizing factor.”. Br. J. Cancer 86 (3): 424–8. DOI:10.1038/sj.bjc.6600086. PMC 2375201. PMID 11875710. 

Spoljašnje veze

  • „β3-adrenoceptor”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2014-12-30. 
  • p
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  • u
Klasa A: Rodopsinu slični
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat  • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6)  • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
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)