Beta-3 adrenergički receptor
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
уредиDejstva 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
уредиBeta adrenergički receptori učestvuju u epinefrinom i norepinefrinom indukovanoj aktivaciji adenilat ciklaze putem aktivacije G proteina Gs tipa.[5]
Agonisti
уреди- 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
уреди- Za SR 59230A se mislilo da je selektivni β3 antagonist[11] ali je naknadno utvrđeno da je takođe antagonist α1 receptora.[12]
Interakcije
уредиZa beta-3 adrenergički receptor je pokazano da interaguje sa Src.[13]
Reference
уреди- ^ „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
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- 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.
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- 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
уреди- „β3-adrenoceptor”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 30. 12. 2014. г.