Beta-3 adrenergički receptor

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Beta-3 adrenergički receptor
Identifikatori
Simboli	ADRB3; BETA3AR
Vanjski ID	OMIM: 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
Vrsta	Čovek	Miš
Entrez	155	11556
Ensembl	ENSG00000188778	ENSMUSG00000031489
UniProt	P13945	Q3UP63
RefSeq (mRNA)	NM_000025	NM_013462
RefSeq (protein)	NP_000016	NP_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:

• Povišenje stepena lipolize u adipoznom tkivu.^[2]
• Termogeneza u skeletalnim mišićima^[3]

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 G_s tipa.^[5]

Agonisti

• Amibegron (SR-58611A)^[6][7]

• Solabegron (GW-427,353)^[8]

• Nebivolol

• 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. 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.