Beta-1 adrenergički receptor

Adrenergički, beta-1, receptor
Adrenergički, beta-1, receptor
Identifikatori
Simboli	ADRB1; ADRB1R; B1AR; BETA1AR; RHR
Vanjski ID	OMIM: 109630 MGI: 87937 HomoloGene: 20171 IUPHAR: β1-adrenoceptor GeneCards: ADRB1 Gene
Ontologija gena
Molekularna funkcija	• rodopsinu-slična receptorska aktivnost; • receptorska aktivnost; • adrenoceptorska aktivnost; • beta1-adrenergička receptorska aktivnost; • proteinsko vezivanje;
Celularna komponenta	• membranska frakcija; • ćelijska membrana; • integralno sa ćelijskom membranom; • membrana; • integralno sa membranom;
Biološki proces	• pozitivna regulacija brzine kontrakcija srca epinefrin-norepinefrinom; • povišenje jačine srčanih kontrakcija epinefrin-norepinefrinom; • dijetom indukovana termogeneza; • norepinefrin-epinefrinska vazodilacija tokom regulacije krvnog pritiska; • prenos signala; • signalni put G-protein spregnutog receptora; • aktivacija adenilat ciklaze; • respons na hladnoću; • stvaranje toplote; • negativna regulacija veličine tela; • odgovor na strah; • diferencijacija smeđih masnih ćelija;
Pregled RNK izražavanja
	podaci
Ortolozi
Vrsta	Čovek
Entrez	153
Ensembl	ENSG00000043591
UniProt	P08588
RefSeq (mRNA)	NM_000684
RefSeq (protein)	NP_000675
Lokacija (UCSC)	Chr 10:; 115.79 - 115.8 Mb
PubMed pretraga	[1]

Beta-1 adrenergički receptor (β₁ adrenoreceptor), ili ADRB1, je beta-adrenergički receptor. ADRB1 je takođe oznaka za ljudski gen koji ga kodira.^[1] On je G-protein spregnuti receptor koji vezuje Gs heterotrimerni G protein.

Receptor

Dejstva

Dejstva β₁ receptora obuhvataju:

stimuliše viskozne, amilazom-zasićene sekrecije pljuvačnih žlezda^[2]
Povećava srčani izlaz
- Povećava brzinu srca^[3]
- Povećava kontraktilnost atrijalnog miokarda.
- Povećava kontraktilnost^[3] ventrikularnog miokarda.
- Povećava provođenje^[3] atrioventrikularnog čvora (AV čvor)
Oslobađanje renina iz jukstaglomerularnih ćelija^[3].
Lipoliza u adipoznom tkivu^[3].
Receptor je takođe prisutan u cerebralnom korteksu.

Agonisti

Izoprenalin ima veći afinitet za β₁ od noradrenalina, koji se vezuje sa većim afinitetom od adrenalina. Selektivni agonisti beta-1 receptora su:

Antagonisti

β1-selektivni antagonisti (Beta blokatori) su:

Acebutolol (u hipertenziji, angini pektoris i aritmijama)
Atenolol^[2] (u hipertenziji, koronarnoj arterijskoj bolesti, aritmijama i srčanom udaru)
Betaksolol (u hipertenziji i glaukomu)
Bisoprolol^[5] (u hipertenziji, koronarnoj arterijskoj bolesti, aritmijama, srčanom udaru i ishemijskom oboljenju srca)
Esmolol (aritmije)
Metoprolol^[2] (u hipertenziji, koronarnoj arterijskoj bolesti, srčanom udaru i srčanoj insuficijenciji)
Nebivolol (u hipertenziji)

Mehanizam

G_s uzrokuje aktivaciju adenilat ciklaze, što dovodi do povećanja cAMP koncentracije.

Gen

Ustanovljeno je da specifični polimorfizmi ovog gena utiču na brzinu rada srca i da mogu da imaju udela u srčanoj insuficijenciji.^[1]

Interakcije

Za beta-1 adrenergički receptor je pokazano da interaguje sa DLG4^[6] i GIPC1.^[7]

Reference

^ ^а ^б „Entrez Gene: ADRB1 adrenergic, beta-1-, receptor”.
^ ^а ^б ^в ^г Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. стр. 163. ISBN 978-0-443-07145-4.
^ ^а ^б ^в ^г ^д Fitzpatrick, David; Purves, Dale; Augustine, George (2004). „Table 20:2”. Neuroscience (Third изд.). Sunderland, Mass: Sinauer. ISBN 978-0-87893-725-7.
^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4. Page 163
^ American Society of Health-System Pharmacists, Inc. (1. 1. 2005). „Bisoprolol”. MedlinePlus Drug Information. U.S. National Library of Medicine, National Institutes of Health. Архивирано из оригинала 20. 5. 2008. г. Приступљено 6. 6. 2008.
^ Hu, L A; Tang Y; Miller W E; Cong M; Lau A G; Lefkowitz R J; Hall R A (2000). „beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors”. J. Biol. Chem. UNITED STATES. 275 (49): 38659—66. ISSN 0021-9258. PMID 10995758. doi:10.1074/jbc.M005938200.
^ Hu, Liaoyuan A; Chen Wei; Martin Negin P; Whalen Erin J; Premont Richard T; Lefkowitz Robert J (2003). „GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation”. J. Biol. Chem. United States. 278 (28): 26295—301. ISSN 0021-9258. PMID 12724327. doi:10.1074/jbc.M212352200.

Literatura

Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4.

Dodatna literatura

Frielle T, Kobilka B, Lefkowitz RJ, Caron MG (1989). „Human beta 1- and beta 2-adrenergic receptors: structurally and functionally related receptors derived from distinct genes.”. Trends Neurosci. 11 (7): 321—4. PMID 2465637. doi:10.1016/0166-2236(88)90095-1.
Muszkat M (2007). „Interethnic differences in drug response: the contribution of genetic variability in beta adrenergic receptor and cytochrome P4502C9.”. Clin. Pharmacol. Ther. 82 (2): 215—8. PMID 17329986. doi:10.1038/sj.clpt.6100142.
Yang-Feng TL; Xue FY; Zhong WW (1990). „Chromosomal organization of adrenergic receptor genes.”. Proc. Natl. Acad. Sci. U.S.A. 87 (4): 1516—1520. PMC 53506  . PMID 2154750. doi:10.1073/pnas.87.4.1516.
Forse RA, Leibel R, Gagner M (1989). „The effect of Escherichia coli endotoxin on the adrenergic control of lipolysis in the human adipocyte.”. J. Surg. Res. 46 (1): 41—8. PMID 2536864. doi:10.1016/0022-4804(89)90180-7.
Frielle T; Collins S; Daniel KW (1987). „Cloning of the cDNA for the human beta 1-adrenergic receptor.”. Proc. Natl. Acad. Sci. U.S.A. 84 (22): 7920—7924. PMC 299447  . PMID 2825170. doi:10.1073/pnas.84.22.7920.
Stiles GL; Strasser RH; Lavin TN (1983). „The cardiac beta-adrenergic receptor. Structural similarities of beta 1 and beta 2 receptor subtypes demonstrated by photoaffinity labeling.”. J. Biol. Chem. 258 (13): 8443—8449. PMID 6305985.
Hoehe MR; Otterud B; Hsieh WT (1995). „Genetic mapping of adrenergic receptor genes in humans.”. J. Mol. Med. 73 (6): 299—306. PMID 7583452. doi:10.1007/BF00231616.
Elies R; Ferrari I; Wallukat G (1996). „Structural and functional analysis of the B cell epitopes recognized by antireceptor autoantibodies in patients with Chagas' disease.”. J. Immunol. 157 (9): 4203—4211. PMID 8892658.
Oldenhof J; Vickery R; Anafi M (1998). „SH3 binding domains in the dopamine D4 receptor.”. Biochemistry. 37 (45): 15726—36. PMID 9843378. doi:10.1021/bi981634.
Mason DA, Moore JD, Green SA, Liggett SB (1999). „A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor.”. J. Biol. Chem. 274 (18): 12670—4. PMID 10212248. doi:10.1074/jbc.274.18.12670.
Moore JD; Mason DA; Green SA (1999). „Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms: analysis of c145A>G and c1165G>C.”. Hum. Mutat. 14 (3): 271. PMID 10477438. doi:10.1002/(SICI)1098-1004(1999)14:3<271::AID-HUMU14>3.0.CO;2-Q.
Tang Y; Hu LA; Miller WE (1999). „Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor.”. Proc. Natl. Acad. Sci. U.S.A. 96 (22): 12559—64. PMC 22990  . PMID 10535961. doi:10.1073/pnas.96.22.12559.
Podlowski S; Wenzel K; Luther HP (2000). „Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?”. J. Mol. Med. 78 (2): 87—93. PMID 10794544. doi:10.1007/s001090000080.
Shiina T, Kawasaki A, Nagao T, Kurose H (2000). „Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors.”. J. Biol. Chem. 275 (37): 29082—90. PMID 10862778. doi:10.1074/jbc.M909757199.
Hu LA; Tang Y; Miller WE (2001). „beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors.”. J. Biol. Chem. 275 (49): 38659—66. PMID 10995758. doi:10.1074/jbc.M005938200.
Börjesson M, Magnusson Y, Hjalmarson A, Andersson B (2001). „A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure.”. Eur. Heart J. 21 (22): 1853—1858. PMID 11052857. doi:10.1053/euhj.1999.1994.
Xu J; Paquet M; Lau AG (2001). „beta 1-adrenergic receptor association with the synaptic scaffolding protein membrane-associated guanylate kinase inverted-2 (MAGI-2). Differential regulation of receptor internalization by MAGI-2 and PSD-95.”. J. Biol. Chem. 276 (44): 41310—7. PMID 11526121. doi:10.1074/jbc.M107480200.
Hu LA; Chen W; Premont RT (2002). „G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95.”. J. Biol. Chem. 277 (2): 1607—1613. PMID 11700307. doi:10.1074/jbc.M107297200.
Ranade K; Jorgenson E; Sheu WH (2002). „A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate.”. Am. J. Hum. Genet. 70 (4): 935—42. PMC 379121  . PMID 11854867. doi:10.1086/339621.
Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. стр. 163. ISBN 978-0-443-07145-4.
Fitzpatrick, David; Purves, Dale; Augustine, George (2004). „Table 20:2”. Neuroscience (Third изд.). Sunderland, Mass: Sinauer. ISBN 978-0-87893-725-7.

Spoljašnje veze

„β₁-adrenoceptor”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 06. 06. 2015. г.

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

[Rang163-2] а ^б ^в ^г Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. стр. 163. ISBN 978-0-443-07145-4.

[purves-3] а ^б ^в ^г ^д Fitzpatrick, David; Purves, Dale; Augustine, George (2004). „Table 20:2”. Neuroscience (Third изд.). Sunderland, Mass: Sinauer. ISBN 978-0-87893-725-7.

[autogenerated1-4] Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4. Page 163

[bisoprolol-5] American Society of Health-System Pharmacists, Inc. (1. 1. 2005). „Bisoprolol”. MedlinePlus Drug Information. U.S. National Library of Medicine, National Institutes of Health. Архивирано из оригинала 20. 5. 2008. г. Приступљено 6. 6. 2008.

[pmid10995758-6] Hu, L A; Tang Y; Miller W E; Cong M; Lau A G; Lefkowitz R J; Hall R A (2000). „beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors”. J. Biol. Chem. UNITED STATES. 275 (49): 38659—66. ISSN 0021-9258. PMID 10995758. doi:10.1074/jbc.M005938200.

[pmid12724327-7] Hu, Liaoyuan A; Chen Wei; Martin Negin P; Whalen Erin J; Premont Richard T; Lefkowitz Robert J (2003). „GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation”. J. Biol. Chem. United States. 278 (28): 26295—301. ISSN 0021-9258. PMID 12724327. doi:10.1074/jbc.M212352200.

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