Beta-3 adrenergički receptor

Beta-3 adrenergički receptor
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
Entrez	155
Ensembl	ENSG00000188778
UniProt	P13945
RefSeq (mRNA)	NM_000025
RefSeq (protein)	NP_000016
Lokacija (UCSC)	Chr 8:; 37.94 - 37.94 Mb
PubMed pretraga	[1]

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

^ „Entrez Gene: ADRB1 adrenergic, beta-1-, receptor”.
^ ^а ^б Ferrer-Lorente R, Cabot C, Fernández-López JA, Alemany M (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. PMID 15935402. doi:10.1016/j.lfs.2005.04.008.
^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4. Page 163
^ Masaaki Sawa; Hiroshi Harada (2006). „Recent Developments in the Design of Orally Bioavailable β3-Adrenergic Receptor Agonists”. Current Medicinal Chemistry. 13 (1): 25—37. PMID 16457637. doi:10.2174/092986706775198006.
^ „Entrez Gene: ADRB3 adrenergic, beta-3-, receptor”.
^ Consoli D, Leggio GM, Mazzola C, Micale V, Drago F (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. PMID 17669397. doi:10.1016/j.ejphar.2007.06.048.
^ Overstreet DH, Stemmelin J, Griebel G (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. PMID 18358519. doi:10.1016/j.pbb.2008.02.020.
^ Hicks A, McCafferty GP, Riedel E, Aiyar N, Pullen M, Evans C, Luce TD, Coatney RW, Rivera GC, Westfall TD, Hieble JP (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. PMID 17626794. doi:10.1124/jpet.107.125757.
^ 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.
^ 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. PMID 18304529. doi:10.1016/j.ejphar.2008.01.028.
^ 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.
^ Bexis S, Docherty JR (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. PMC 2795232 . PMID 19422394. doi:10.1111/j.1476-5381.2009.00186.x.
^ Cao W, Luttrell LM, Medvedev AV, Pierce KL, Daniel KW, Dixon TM, Lefkowitz RJ, Collins S (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. ISSN 0021-9258. PMID 11013230. doi:10.1074/jbc.C000592200.

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 (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 (1989). „Molecular characterization of the human beta 3-adrenergic receptor.”. Science. 245 (4922): 1118—21. PMID 2570461. doi:10.1126/science.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 (1995). „Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain.”. Brain Res. Mol. Brain Res. 29 (2): 369—75. PMID 7609625. doi:10.1016/0169-328X(94)00274-I.
Clément K; Vaisse C; Manning BS (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. PMID 7609752. doi:10.1056/NEJM199508103330605.
Dib A; Adélaïde J; Chaffanet M (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. PMID 8011597. doi:10.1016/0263-7855(94)80004-9.
Wilkie TM; Chen Y; Gilbert DJ (1994). „Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors.”. Genomics. 18 (2): 175—84. PMID 8288218. doi:10.1006/geno.1993.1452.
Krief S; Lönnqvist F; Raimbault S (1993). „Tissue distribution of beta 3-adrenergic receptor mRNA in man.”. J. Clin. Invest. 91 (1): 344—9. PMC 330032 . PMID 8380813. doi:10.1172/JCI116191.
van Spronsen A; Nahmias C; Krief S (1993). „The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes.”. Eur. J. Biochem. 213 (3): 1117—24. PMID 8389293. doi:10.1111/j.1432-1033.1993.tb17861.x.
Lelias JM; Kaghad M; Rodriguez M (1993). „Molecular cloning of a human beta 3-adrenergic receptor cDNA.”. FEBS Lett. 324 (2): 127—30. PMID 8389717. doi:10.1016/0014-5793(93)81377-C.
Candelore MR; Deng L; Tota LM (1996). „Pharmacological characterization of a recently described human beta 3-adrenergic receptor mutant.”. Endocrinology. 137 (6): 2638—41. PMID 8641219. doi:10.1210/en.137.6.2638.
Fujisawa T; Ikegami H; Yamato E (1996). „Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain.”. Diabetologia. 39 (3): 349—52. PMID 8721782. doi:10.1007/BF00418352.
Higashi K; Ishikawa T; Ito T (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. PMID 9126344. doi:10.1006/bbrc.1997.6339.
Hoffstedt J; Poirier O; Thörne A (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. PMID 9892244. doi:10.2337/diabetes.48.1.203.
Halushka MK; Fan JB; Bentley K (1999). „Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.”. Nat. Genet. 22 (3): 239—47. PMID 10391210. doi:10.1038/10297.
Kimura K; Sasaki N; Asano A (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. PMID 10786926. doi:10.1055/s-2007-978597.
Cao W; Luttrell LM; Medvedev AV (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. PMID 11013230. doi:10.1074/jbc.C000592200.
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. PMC 2375201 . PMID 11875710. doi:10.1038/sj.bjc.6600086.

Spoljašnje veze

„β₃-adrenoceptor”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 30. 12. 2014. г.

[entrez-1] „Entrez Gene: ADRB1 adrenergic, beta-1-, receptor”.

[pmid15935402-2] а ^б Ferrer-Lorente R, Cabot C, Fernández-López JA, Alemany M (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. PMID 15935402. doi:10.1016/j.lfs.2005.04.008.

[Rang163-3] Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4. Page 163

[pmid16457637-4] Masaaki Sawa; Hiroshi Harada (2006). „Recent Developments in the Design of Orally Bioavailable β3-Adrenergic Receptor Agonists”. Current Medicinal Chemistry. 13 (1): 25—37. PMID 16457637. doi:10.2174/092986706775198006.

[autogenerated1-5] „Entrez Gene: ADRB3 adrenergic, beta-3-, receptor”.

[pmid17669397-6] Consoli D, Leggio GM, Mazzola C, Micale V, Drago F (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. PMID 17669397. doi:10.1016/j.ejphar.2007.06.048.

[pmid18358519-7] Overstreet DH, Stemmelin J, Griebel G (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. PMID 18358519. doi:10.1016/j.pbb.2008.02.020.

[pmid17626794-8] Hicks A, McCafferty GP, Riedel E, Aiyar N, Pullen M, Evans C, Luce TD, Coatney RW, Rivera GC, Westfall TD, Hieble JP (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. PMID 17626794. doi:10.1124/jpet.107.125757.

[pmid12324291-9] 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. PMID 18304529. doi:10.1016/j.ejphar.2008.01.028.

[pmid8569714-11] 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.

[pmid19422394-12] Bexis S, Docherty JR (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. PMC 2795232 . PMID 19422394. doi:10.1111/j.1476-5381.2009.00186.x.

[pmid11013230-13] Cao W, Luttrell LM, Medvedev AV, Pierce KL, Daniel KW, Dixon TM, Lefkowitz RJ, Collins S (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. ISSN 0021-9258. PMID 11013230. doi:10.1074/jbc.C000592200.

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