Beta-1 adrenergic receptor

Adrenoceptor beta 1

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2LSQ

Identifiers

Symbols

ADRB1 ; ADRB1R; B1AR; BETA1AR; RHR

External IDs

OMIM: 109630 MGI: 87937 HomoloGene: 20171 IUPHAR: 28 ChEMBL: 213 GeneCards: ADRB1 Gene

Gene ontology
Molecular function	• beta-adrenergic receptor activity • beta1-adrenergic receptor activity • receptor signaling protein activity • Ras guanyl-nucleotide exchange factor activity • protein binding • PDZ domain binding • alpha-2A adrenergic receptor binding • protein heterodimerization activity • epinephrine binding • norepinephrine binding
Cellular component	• early endosome • plasma membrane • integral component of plasma membrane
Biological process	• temperature homeostasis • 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 • cell-cell signaling • response to cold • positive regulation of cAMP biosynthetic process • heat generation • intracellular signal transduction • negative regulation of multicellular organism growth • fear response • positive regulation of GTPase activity • positive regulation of cAMP-mediated signaling • brown fat cell differentiation • adenylate cyclase-activating adrenergic receptor signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

153

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 10:
114.04 – 114.05 Mb

Chr 19:
56.72 – 56.72 Mb

PubMed search

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 and is expressed predominantly in cardiac tissue.

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 adrenaline, which, in turn, binds with higher affinity than noradrenaline at physiologic concentrations. 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)
Vortioxetine (antidepressant)

Mechanism

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

Gene

Specific polymorphisms in the ADRB1 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] Interaction between testosterone and β-1 ARs have been shown in anxiolytic behaviors in the basolateral amygdala.^[7]

References

1 2 "Entrez Gene: ADRB1 adrenergic, beta-1-, receptor".
1 2 3 4 5 Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
1 2 3 4 5 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. Retrieved 2008-06-06.
↑ Hu LA, Tang Y, Miller WE, Cong M, Lau AG, Lefkowitz RJ, Hall RA (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". The Journal of Biological Chemistry 275 (49): 38659–66. doi:10.1074/jbc.M005938200. PMID 10995758.
↑ Hu LA, Chen W, Martin NP, Whalen EJ, Premont RT, Lefkowitz RJ (Jul 2003). "GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation". The Journal of Biological Chemistry 278 (28): 26295–301. doi:10.1074/jbc.M212352200. PMID 12724327.
↑ Mard-Soltani M, Kesmati M, Khajehpour L, Rasekh A, Shamshirgar-Zadeh A (April 2012). "Interaction between Anxiolytic Effects of Testosterone and β-1 Adrenoceptors of Basolateral Amygdala". International Journal of Pharmacology 8 (5): 344–354. doi:10.3923/ijp.2012.344.354.

External links

"β₁-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

Frielle T, Kobilka B, Lefkowitz RJ, Caron MG (Jul 1988). "Human beta 1- and beta 2-adrenergic receptors: structurally and functionally related receptors derived from distinct genes". Trends in Neurosciences 11 (7): 321–4. doi:10.1016/0166-2236(88)90095-1. PMID 2465637.
Muszkat M (Aug 2007). "Interethnic differences in drug response: the contribution of genetic variability in beta adrenergic receptor and cytochrome P4502C9". Clinical Pharmacology and Therapeutics 82 (2): 215–8. doi:10.1038/sj.clpt.6100142. PMID 17329986.
Yang-Feng TL, Xue FY, Zhong WW, Cotecchia S, Frielle T, Caron MG, Lefkowitz RJ, Francke U (Feb 1990). "Chromosomal organization of adrenergic receptor genes". Proceedings of the National Academy of Sciences of the United States of America 87 (4): 1516–20. doi:10.1073/pnas.87.4.1516. PMC: 53506. PMID 2154750.
Forse RA, Leibel R, Gagner M (Jan 1989). "The effect of Escherichia coli endotoxin on the adrenergic control of lipolysis in the human adipocyte". The Journal of Surgical Research 46 (1): 41–8. doi:10.1016/0022-4804(89)90180-7. PMID 2536864.
Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ, Kobilka BK (Nov 1987). "Cloning of the cDNA for the human beta 1-adrenergic receptor". Proceedings of the National Academy of Sciences of the United States of America 84 (22): 7920–4. doi:10.1073/pnas.84.22.7920. PMC: 299447. PMID 2825170.
Stiles GL, Strasser RH, Lavin TN, Jones LR, Caron MG, Lefkowitz RJ (Jul 1983). "The cardiac beta-adrenergic receptor. Structural similarities of beta 1 and beta 2 receptor subtypes demonstrated by photoaffinity labeling". The Journal of Biological Chemistry 258 (13): 8443–9. PMID 6305985.
Hoehe MR, Otterud B, Hsieh WT, Martinez MM, Stauffer D, Holik J, Berrettini WH, Byerley WF, Gershon ES, Lalouel JM (Jun 1995). "Genetic mapping of adrenergic receptor genes in humans". Journal of Molecular Medicine 73 (6): 299–306. doi:10.1007/BF00231616. PMID 7583452.
Elies R, Ferrari I, Wallukat G, Lebesgue D, Chiale P, Elizari M, Rosenbaum M, Hoebeke J, Levin MJ (Nov 1996). "Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with Chagas' disease". Journal of Immunology 157 (9): 4203–11. PMID 8892658.
Oldenhof J, Vickery R, Anafi M, Oak J, Ray A, Schoots O, Pawson T, von Zastrow M, Van Tol HH (Nov 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 (Apr 1999). "A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor". The Journal of Biological Chemistry 274 (18): 12670–4. doi:10.1074/jbc.274.18.12670. PMID 10212248.
Moore JD, Mason DA, Green SA, Hsu J, Liggett SB (Sep 1999). "Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms: analysis of c145A>G and c1165G>C". Human Mutation 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, Ringstad N, Hall RA, Pitcher JA, DeCamilli P, Lefkowitz RJ (Oct 1999). "Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor". Proceedings of the National Academy of Sciences of the United States of America 96 (22): 12559–64. doi:10.1073/pnas.96.22.12559. PMC: 22990. PMID 10535961.
Podlowski S, Wenzel K, Luther HP, Müller J, Bramlage P, Baumann G, Felix SB, Speer A, Hetzer R, Köpke K, Hoehe MR, Wallukat G (2000). "Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?". Journal of Molecular Medicine 78 (2): 87–93. doi:10.1007/s001090000080. PMID 10794544.
Shiina T, Kawasaki A, Nagao T, Kurose H (Sep 2000). "Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors". The Journal of Biological Chemistry 275 (37): 29082–90. doi:10.1074/jbc.M909757199. PMID 10862778.
Hu LA, Tang Y, Miller WE, Cong M, Lau AG, Lefkowitz RJ, Hall RA (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". The Journal of Biological Chemistry 275 (49): 38659–66. doi:10.1074/jbc.M005938200. PMID 10995758.
Börjesson M, Magnusson Y, Hjalmarson A, Andersson B (Nov 2000). "A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure". European Heart Journal 21 (22): 1853–8. doi:10.1053/euhj.1999.1994. PMID 11052857.
Xu J, Paquet M, Lau AG, Wood JD, Ross CA, Hall RA (Nov 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". The Journal of Biological Chemistry 276 (44): 41310–7. doi:10.1074/jbc.M107480200. PMID 11526121.
Hu LA, Chen W, Premont RT, Cong M, Lefkowitz RJ (Jan 2002). "G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95". The Journal of Biological Chemistry 277 (2): 1607–13. doi:10.1074/jbc.M107297200. PMID 11700307.
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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

Adhesion	ADGRG (1 2 3 4 5 6 7)

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 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

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

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