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 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:

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

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. ^ 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. 
  3. ^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4.  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. PMID 16457637. doi:10.2174/092986706775198006. 
  5. ^ „Entrez Gene: ADRB3 adrenergic, beta-3-, receptor”. 
  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. 
  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. 
  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. 
  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. 
  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 (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 Слободан приступ. PMID 19422394. doi:10.1111/j.1476-5381.2009.00186.x. 
  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. 

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 Слободан приступ. 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 Слободан приступ. 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 Слободан приступ. 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. 
  • п
  • р
  • у
Klasa A: Rodopsinu slični
Neurotransmiter
Adrenergički
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Purinski
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
Serotoninski
(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
Eikozanoidni
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
Neuropeptidni
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
Orfan
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
Orfan
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
Ukus
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
Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A • GPR (156, 158, 179) • RAIG (1, 2, 3, 4) • VNR (1, 2, 3, 5)
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni