Beta-1 adrenergic receptor

Adrenergic, beta-1-, receptor

Identifiers

ADRB1; ADRB1R; B1AR; BETA1AR; RHR

External IDs

OMIM: 109630 MGI: 87937 HomoloGene: 20171 IUPHAR: β₁-adrenoceptor GeneCards: ADRB1 Gene

Gene Ontology
Molecular function	• receptor activity • G-protein coupled receptor activity • beta-adrenergic receptor activity • beta1-adrenergic receptor activity • protein binding • drug binding • alpha-2A adrenergic receptor binding • dopamine binding • protein heterodimerization activity • epinephrine binding • norepinephrine binding
Cellular component	• membrane fraction • microsome • plasma membrane • plasma membrane • integral to plasma membrane
Biological process	• positive regulation of heart rate by epinephrine-norepinephrine • positive regulation of the force of heart contraction by epinephrine-norepinephrine • diet induced thermogenesis • vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure • activation of adenylate cyclase activity by G-protein signaling pathway • activation of adenylate cyclase activity • response to cold • positive regulation of cAMP biosynthetic process • heat generation • negative regulation of multicellular organism growth • fear response • brown fat cell differentiation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 10:
115.8 – 115.81 Mb

Chr 19:
56.8 – 56.8 Mb

PubMed search

[1]

[2]

The beta-1 adrenergic receptor (β₁ adrenoreceptor), also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it.^[1] It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein.

1 Receptor
2 Gene
3 Interactions
4 See also
5 References
6 External links
7 Further reading

Receptor

Actions

Actions of the β₁ receptor include:

stimulate viscous, amylase-filled secretions from salivary glands^[2]
Increase cardiac output
- Increase heart rate ^[3] in sinoatrial node (SA node) (chronotropic effect)
- Increase atrial cardiac muscle contractility. (inotropic effect)
- Increases contractility and automaticity^[3] of ventricular cardiac muscle.
- Increases conduction and automaticity^[3] of atrioventricular node (AV node)

Renin release from juxtaglomerular cells^[3].
Lipolysis in adipose tissue^[3].
Receptor also present in cerebral cortex.

Agonists

Isoprenaline has higher affinity for β₁ than noradrenaline, which, in turn, binds with higher affinity than adrenaline. Selective agonists to the beta-1 receptor are:

Antagonists

(Beta blockers) β1-selective ones are:

Acebutolol (in hypertension, angina pectoris and arrhythmias)
Atenolol^[2] (in hypertension, coronary heart disease, arrhythmias and myocardial infarction)
Betaxolol (in hypertension and glaucoma)
Bisoprolol^[4] (in hypertension, coronary heart disease, arrhythmias, myocardial infarction and ischemic heart diseases)
Esmolol (in arrhythmias)
Metoprolol^[2] (in hypertension, coronary heart disease, myocardial infarction and heart failure)
Nebivolol (in hypertension)

Mechanism

G_s renders adenylate cyclase activated, resulting in increase of cAMP.

Gene

Specific polymorphisms in this gene have been shown to affect the resting heart rate and can be involved in heart failure.^[1]

Interactions

Beta-1 adrenergic receptor has been shown to interact with DLG4^[5] and GIPC1.^[6]

References

^ ^a ^b "Entrez Gene: ADRB1 adrenergic, beta-1-, receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=153.
^ ^a ^b ^c ^d ^e Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
^ ^a ^b ^c ^d ^e Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0.
^ American Society of Health-System Pharmacists, Inc. (2005-01-01). "Bisoprolol". MedlinePlus Drug Information. U.S. National Library of Medicine, National Institutes of Health. Archived from the original on 2008-05-20. http://web.archive.org/web/20080520211346/http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a693024.html. Retrieved 2008-06-06.
^ Hu, L A; Tang Y, Miller W E, Cong M, Lau A G, Lefkowitz R J, Hall R A (Dec. 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. doi:10.1074/jbc.M005938200. ISSN 0021-9258. PMID 10995758.
^ Hu, Liaoyuan A; Chen Wei, Martin Negin P, Whalen Erin J, Premont Richard T, Lefkowitz Robert J (Jul. 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. doi:10.1074/jbc.M212352200. ISSN 0021-9258. PMID 12724327.

External links

"β₁-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2187.

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. doi:10.1016/0166-2236(88)90095-1. PMID 2465637.
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. doi:10.1038/sj.clpt.6100142. PMID 17329986.
Yang-Feng TL, Xue FY, Zhong WW, et al. (1990). "Chromosomal organization of adrenergic receptor genes.". Proc. Natl. Acad. Sci. U.S.A. 87 (4): 1516–1520. doi:10.1073/pnas.87.4.1516. PMC 53506. PMID 2154750. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=53506.
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. doi:10.1016/0022-4804(89)90180-7. PMID 2536864.
Frielle T, Collins S, Daniel KW, et al. (1987). "Cloning of the cDNA for the human beta 1-adrenergic receptor.". Proc. Natl. Acad. Sci. U.S.A. 84 (22): 7920–7924. doi:10.1073/pnas.84.22.7920. PMC 299447. PMID 2825170. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=299447.
Stiles GL, Strasser RH, Lavin TN, et al. (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, et al. (1995). "Genetic mapping of adrenergic receptor genes in humans.". J. Mol. Med. 73 (6): 299–306. doi:10.1007/BF00231616. PMID 7583452.
Elies R, Ferrari I, Wallukat G, et al. (1996). "Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with Chagas' disease.". J. Immunol. 157 (9): 4203–4211. PMID 8892658.
Oldenhof J, Vickery R, Anafi M, et al. (1998). "SH3 binding domains in the dopamine D4 receptor.". Biochemistry 37 (45): 15726–36. doi:10.1021/bi981634. PMID 9843378.
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. doi:10.1074/jbc.274.18.12670. PMID 10212248.
Moore JD, Mason DA, Green SA, et al. (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. doi:10.1002/(SICI)1098-1004(1999)14:3<271::AID-HUMU14>3.0.CO;2-Q. PMID 10477438.
Tang Y, Hu LA, Miller WE, et al. (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. doi:10.1073/pnas.96.22.12559. PMC 22990. PMID 10535961. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22990.
Podlowski S, Wenzel K, Luther HP, et al. (2000). "Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?". J. Mol. Med. 78 (2): 87–93. doi:10.1007/s001090000080. PMID 10794544.
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. doi:10.1074/jbc.M909757199. PMID 10862778.
Hu LA, Tang Y, Miller WE, et al. (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. doi:10.1074/jbc.M005938200. PMID 10995758.
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. doi:10.1053/euhj.1999.1994. PMID 11052857.
Xu J, Paquet M, Lau AG, et al. (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. doi:10.1074/jbc.M107480200. PMID 11526121.
Hu LA, Chen W, Premont RT, et al. (2002). "G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95.". J. Biol. Chem. 277 (2): 1607–1613. doi:10.1074/jbc.M107297200. PMID 11700307.
Ranade K, Jorgenson E, Sheu WH, et al. (2002). "A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate.". Am. J. Hum. Genet. 70 (4): 935–42. doi:10.1086/339621. PMC 379121. PMID 11854867. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=379121.

Cell surface receptor: G protein-coupled receptors

Class A:
Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A, B, D) · α2 (A, B, C) · β1 · β2 · β3

Purinergic	Adenosine (A1, A2A, A2B, A3) · P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)

Serotonin	(all but 5-HT3) 5-HT1 (A, B, D, E, F) · 5-HT2 (A, B, C) · 5-HT (4, 5A, 6, 7)

Other	Acetylcholine (M1, M2, M3, M4, M5) · Dopamine (D1, D2, D3, D4, D5) · Histamine (H1, H2, H3, H4) · Melatonin (1A, 1B, 1C) · TAAR (1, 2, 3, 5, 6, 8, 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1, 2) · LTB4 (1, 2) · FPRL1 · OXE · Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) · Prostacyclin · Thromboxane

Other	Bile acid · Cannabinoid (CB1, CB2, GPR (18, 55, 119)) · EBI2 · Estrogen · Free fatty acid (1, 2, 3, 4) · Lactate · Lysophosphatidic acid (1, 2, 3, 4, 5, 6) · Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) · Niacin (1, 2) · Oxoglutarate · PAF · Sphingosine-1-phosphate (1, 2, 3, 4, 5) · Succinate

Peptide

Neuropeptide	B/W (1, 2) · FF (1, 2) · S · Y (1, 2, 4, 5) · Neuromedin (B, U (1, 2)) · Neurotensin (1, 2)

Other	Anaphylatoxin (C3a, C5a) · Angiotensin (1, 2) · Apelin · Bombesin (BRS3, GRPR, NMBR) · Bradykinin (B1, B2) · Chemokine · Cholecystokinin (A, B) · Endothelin (A, B) · Formyl peptide (1, 2, 3) · FSH · Galanin (1, 2, 3) · GHB receptor · Gonadotropin-releasing hormone (1, 2) · Ghrelin · Kisspeptin · Luteinizing hormone/choriogonadotropin · MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) · Melanocortin (1, 2, 3, 4, 5) · MCHR (1, 2) · Motilin · Opioid (Delta, Kappa, Mu, Nociceptin & Zeta, but not Sigma) · Orexin (1, 2) · Oxytocin · Prokineticin (1, 2) · Prolactin-releasing peptide · Relaxin (1, 2, 3, 4) · Somatostatin (1, 2, 3, 4, 5) · Tachykinin (1, 2, 3) · Thyrotropin · Thyrotropin-releasing hormone · Urotensin-II · Vasopressin (1A, 1B, 2)

Miscellaneous

Orphan	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)

Other	Adrenomedullin · Olfactory · Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) · Protease-activated (1, 2, 3, 4) · SREB (1, 2, 3)

Class B: Secretin like

Orphan	GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)

Other	Brain-specific angiogenesis inhibitor (1, 2, 3) · Cadherin (1, 2, 3) · Calcitonin · CALCRL · CD97 · Corticotropin-releasing hormone (1, 2) · EMR (1, 2, 3) · Glucagon (GR, GIPR, GLP1R, GLP2R) · Growth hormone releasing hormone · PACAPR1 · GPR · Latrophilin (1, 2, 3, ELTD1) · Methuselah-like proteins · Parathyroid hormone (1, 2) · Secretin · Vasoactive intestinal peptide (1, 2)

Class C: Metabotropic
glutamate / pheromone

Taste	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)

Other	Calcium-sensing receptor · GABA B (1, 2) · Glutamate receptor (Metabotropic glutamate (1, 2, 3, 4, 5, 6, 7, 8)) · GPRC6A · GPR (156, 158, 179) · RAIG (1, 2, 3, 4)

Class F:
Frizzled / Smoothened

Frizzled	Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

Smoothened	Smoothened

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)