Skip to main content
SpringerLink
Log in

β-Adrenergic receptor, an essential target in cardiovascular diseases

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

β-Adrenergic receptors (βARs) belong to a large family of cell surface receptors known as G protein–coupled receptors (GPCRs). They are coupled to Gs protein (Gαs) for the activation of adenylyl cyclase (AC) yielding cyclic AMP (CAMP), and this provides valuable responses, which can affect the cardiac function such as injury. The binding of an agonist to βAR enhances conformation changes that lead to the Gαs subtype of heterotrimeric G protein which is the AC stimulatory G protein for activation of CAMP in the cells. However, cardiovascular diseases (CVD) have been reported as having an increased rate of death and β1AR, and β2AR are a promising tool that improves the regulatory function in the cardiovascular system (CVS) via signaling. It increases the Gα level, which activates βAR kinase (βARK) that affects and enhances the progression of heart failure (HF) through the activation of cardiomyocyte βARs. We also explained that an increase in GPCR kinases (GRKs) would practically improve the HF pathogenesis and this occurs via the desensitization of βARs, which causes the loss of contractile reserve. The consistency or overstimulation of catecholamines contributes to CVD such as stroke, HF, and cardiac hypertrophy. When there is a decrease in catecholamine responsiveness, it causes aging in old people because the reduction of βAR sensitivity and density in the myocardium enhances downregulation of βARs to AC in the human heart.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rudomanova V, Blaxall BC (2017) Targeting GPCR-Gβγ-GRK2 signaling as a novel strategy for treating cardiorenal pathologies. Biochim Biophys Acta (BBA) - Mol Basis Dis 1863(8):1883–1892

    CAS  Google Scholar 

  2. Li D, Paterson DJ (2016) Cyclic nucleotide regulation of cardiac sympatho-vagal responsiveness. J Physiol 594(14):3993–4008

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Rankin J, Rowen D, Howe A, Cleland JG, Whitty JA (2019) Valuing health–related quality of life in heart failure: a systematic review of methods to derive quality–adjusted life years (QALYs) in trial-based cost–utility analyses. Heart Fail Rev 24(4): 549–563

    PubMed  PubMed Central  Google Scholar 

  4. Morris JH, Chen L (2019) Exercise training and heart failure: a review of the literature. Card Fail Rev 5(1):57–61

    PubMed  PubMed Central  Google Scholar 

  5. Guha K, McDonagh T (2013) Heart failure epidemiology: European perspective. Curr Cardiol Rev 9(2):123–127

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Chatterjee S, Biondi-Zoccai G, Abbate A, D’Ascenzo F, Castagno D, Van Tassell B, Mukherjee D, Lichstein E (2013) Benefits of β blockers in patients with heart failure and reduced ejection fraction: network meta-analysis. BMj 346:f55

    PubMed  PubMed Central  Google Scholar 

  7. Jeyanantham K, Kotecha D, Thanki D, Dekker R, Lane DA (2017) Effects of cognitive behavioural therapy for depression in heart failure patients: a systematic review and meta-analysis. Heart Fail Rev 22(6):731–741

    PubMed  PubMed Central  Google Scholar 

  8. Nadar SK, Shaikh MM (2019) Biomarkers in routine heart failure clinical care. Card Fail Rev 5(1):50

    PubMed  PubMed Central  Google Scholar 

  9. Madamanchi A (2007) β-Adrenergic receptor signaling in cardiac function and heart failure. McGill J Med 10(2):99

    PubMed  PubMed Central  Google Scholar 

  10. Chen J-Z, Wang J, Xie X-Q (2007) GPCR structure-based virtual screening approach for CB2 antagonist search. J Chem Inf Model 47(4):1626–1637

    CAS  PubMed  Google Scholar 

  11. Shoichet BK, Kobilka BK (2012) Structure-based drug screening for G-protein-coupled receptors. Trends Pharmacol Sci 33(5):268–272

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Jacobson KA (2015) New paradigms in GPCR drug discovery. Biochem Pharmacol 98(4):541–555

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Santulli G (2015) The adrenergic system in cardiovascular metabolism and aging. In: The cardiovascular adrenergic system. Springer, Cham. pp 97–116

    Google Scholar 

  14. Dolatshad NF, Hellen N, Jabbour RJ, Harding SE, Földes G (2015) G-protein coupled receptor signaling in pluripotent stem cell-derived cardiovascular cells: implications for disease modeling. Front Cell Dev Biol 3:76

    PubMed  PubMed Central  Google Scholar 

  15. Woo AYH, Xiao R-P (2012) β-Adrenergic receptor subtype signaling in heart: from bench to bedside. Acta Pharmacol Sin 33(3):335

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Kamal FA, Travers JG, Blaxall BC (2012) G protein–coupled receptor kinases in cardiovascular disease: why “where” matters. Trends Cardiovasc Med 22(8):213–219

    CAS  PubMed  Google Scholar 

  17. Kim YH, Oh SO, Kim CD (2016) Biased agonism of G protein–coupled receptors: a potential therapeutic strategy of cardiovascular diseases. Cardiovascular Pharmacology:Open Access 5(4): 1–7

  18. Cresci S, Kelly RJ, Cappola TP, Diwan A, Dries D, Kardia SL, Dorn GW (2009) Clinical and genetic modifiers of long-term survival in heart failure. J Am Coll Cardiol 54(5):432–444

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Biolo A, Clausell N, Santos KG, Salvaro R, Ashton-Prolla P, Borges A, Rohde LE (2008) Impact of β1-adrenergic receptor polymorphisms on susceptibility to heart failure, arrhythmogenesis, prognosis, and response to beta-blocker therapy. Am J Cardiol 102(6):726–732

    CAS  PubMed  Google Scholar 

  20. Salazar NC, Chen J, Rockman HA (2007) Cardiac GPCRs: GPCR signaling in healthy and failing hearts. Biochim Biophys Acta Biomembr 1768(4):1006–1018

    CAS  Google Scholar 

  21. Ciccarelli M, Sorriento D, Coscioni E, Iaccarino G, Santulli G (2017) Adrenergic receptors. In: Endocrinology of the heart in health and disease. Elsevier, pp 285–315

  22. Corbi G, Conti V, Russomanno G, Longobardi G, Furgi G, Filippelli A, Ferrara N (2013) Adrenergic signaling and oxidative stress: a role for sirtuins? Front Physiol 4:324

    PubMed  PubMed Central  Google Scholar 

  23. Congreve M, Langmead CJ, Mason JS, Marshall FH (2011) Progress in structure based drug design for G protein-coupled receptors. J Med Chem 54(13):4283–4311

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Santulli G, Iaccarino G (2016) Adrenergic signaling in heart failure and cardiovascular aging. Maturitas 93:65–72

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Stern CS, Lebowitz J (2010) Latest drug developments in the field of cardiovascular disease. Int J Angiol 19(03):e100–e105

    PubMed  PubMed Central  Google Scholar 

  26. Sarkhel S, Sharon A, Trivedi V, Maulik PR, Singh MM, Venugopalan P, Ray S (2003) Structure-based drug design: synthesis, crystal structure, biological evaluation and docking studies of mono-and bis-benzo [b] oxepines as non-steroidal estrogens. Bioorg Med Chem 11(23):5025–5033

    CAS  PubMed  Google Scholar 

  27. Rengo G, Lymperopoulos A, Zincarelli C, Femminella G, Liccardo D, Pagano G, De Lucia C, Cannavo A, Gargiulo P, Ferrara N (2012) Blockade of β-adrenoceptors restores the GRK2-mediated adrenal α2-adrenoceptor–catecholamine production axis in heart failure. Br J Pharmacol 166(8):2430–2440

    CAS  PubMed  PubMed Central  Google Scholar 

  28. O’connell J (2000) The economic burden of heart failure. Clin Cardiol 23(S3):III6–III10

    PubMed  Google Scholar 

  29. Siryk-Bathgate A, Dabul S, Lymperopoulos A (2013) Current and future G protein-coupled receptor signaling targets for heart failure therapy. Drug Des Devel Ther 7:1209

    PubMed  PubMed Central  Google Scholar 

  30. Manna M, Niemelä M, Tynkkynen J, Javanainen M, Kulig W, Müller DJ, Rog T, Vattulainen I (2016) Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol. Elife 5:e18432

    PubMed  PubMed Central  Google Scholar 

  31. Vasudevan NT, Mohan ML, Goswami SK, Prasad SVN (2011) Regulation of β-adrenergic receptor function: an emphasis on receptor resensitization. Cell Cycle 10(21):3684–3691

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Cannatà A, Marcon G, Cimmino G, Camparini L, Ciucci G, Sinagra G, Loffredo FS (2017) Role of circulating factors in cardiac aging. J Thorac Dis 9(Suppl 1):S17–S29

    PubMed  PubMed Central  Google Scholar 

  33. White DC, Hata JA, Shah AS, Glower DD, Lefkowitz RJ, Koch WJ (2000) Preservation of myocardial β-adrenergic receptor signaling delays the development of heart failure after myocardial infarction. Proc Natl Acad Sci 97(10):5428–5433

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Park M, Steinberg SF (2018) Carvedilol prevents redox inactivation of cardiomyocyte Β1-adrenergic receptors. JACC Basic Transl Sci 3(4):521–532

    PubMed  PubMed Central  Google Scholar 

  35. Shin E, Ko KS, Rhee BD, Han J, Kim N (2014) Different effects of prolonged β-adrenergic stimulation on heart and cerebral artery. Integr Med Res 3(4):204–210

    PubMed  PubMed Central  Google Scholar 

  36. de Lucia C, Femminella GD, Gambino G, Pagano G, Allocca E, Rengo C, Silvestri C, Leosco D, Ferrara N, Rengo G (2014) Adrenal adrenoceptors in heart failure. Front Physiol 5:246

    PubMed  PubMed Central  Google Scholar 

  37. Strachan RT (2009) P90 ribosomal S6 kinase 2 (RSK2) directly phosphorylates the 5–HT2A serotonin receptor thereby modulating signaling. Case Western Reserve University (Thesis 42103)

  38. Johnson J, Liggett S (2011) Cardiovascular pharmacogenomics of adrenergic receptor signaling: clinical implications and future directions. Clin Pharmacol Ther 89(3):366–378

    CAS  PubMed  Google Scholar 

  39. Fajardo G, Zhao M, Urashima T, Farahani S, Hu D-Q, Reddy S, Bernstein D (2013) Deletion of the β2-adrenergic receptor prevents the development of cardiomyopathy in mice. J Mol Cell Cardiol 63:155–164

    CAS  PubMed  Google Scholar 

  40. De Lucia C, Eguchi A, Koch WJ (2018) New insights in cardiac β-adrenergic signaling during heart failure and aging. Front Pharmacol 9:904

    PubMed  PubMed Central  Google Scholar 

  41. Jones SM, Hiller FC, Jacobi SE, Foreman SK, Pittman LM, Cornett LE (2003) Enhanced β 2-adrenergic receptor (β 2 AR) signaling by adeno-associated viral (AAV)-mediated gene transfer. BMC Pharmacol 3(1):15

    PubMed  PubMed Central  Google Scholar 

  42. Katritch V, Rueda M, Lam PCH, Yeager M, Abagyan R (2010) GPCR 3D homology models for ligand screening: lessons learned from blind predictions of adenosine A2a receptor complex. Proteins: Struct, Funct, Bioinf 78(1):197–211

    CAS  Google Scholar 

  43. Yuzlenko O, Kieć-Kononowicz K (2009) Molecular modeling of A1 and A2A adenosine receptors: comparison of rhodopsin-and β2-adrenergic-based homology models through the docking studies. J Comput Chem 30(1):14–32

    CAS  PubMed  Google Scholar 

  44. Kolb P, Rosenbaum DM, Irwin JJ, Fung JJ, Kobilka BK, Shoichet BK (2009) Structure-based discovery of β2-adrenergic receptor ligands. Proc Natl Acad Sci 106(16):6843–6848

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Corbi G, Conti V, Russomanno G, Rengo G, Vitulli P, Ciccarelli AL, Filippelli A, Ferrara N (2012) Is physical activity able to modify oxidative damage in cardiovascular aging? Oxidative Med Cell Longev 2012:1–6

    Google Scholar 

  46. Samuel CS, Unemori EN, Mookerjee I, Bathgate RA, Layfield SL, Mak J, Tregear GW, Du X-J (2004) Relaxin modulates cardiac fibroblast proliferation, differentiation, and collagen production and reverses cardiac fibrosis in vivo. Endocrinology 145(9):4125–4133

    CAS  PubMed  Google Scholar 

  47. Stallaert W, Dorn JF, Van Der Westhuizen E, Audet M, Bouvier M (2012) Impedance responses reveal β2-adrenergic receptor signaling pluridimensionality and allow classification of ligands with distinct signaling profiles. PLoS One 7(1):e29420

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Bernstein D, Fajardo G, Zhao M (2011) The role of β-adrenergic receptors in heart failure: differential regulation of cardiotoxicity and cardioprotection. Prog Pediatr Cardiol 31(1):35–38

    PubMed  PubMed Central  Google Scholar 

  49. Zhu W, Petrashevskaya N, Ren S, Zhao A, Chakir K, Gao E, Chuprun JK, Wang Y, Talan M, Dorn GW (2012) Gi-biased β2AR signaling links GRK2 upregulation to heart failure novelty and significance. Circ Res 110(2):265–274

    CAS  PubMed  Google Scholar 

  50. Cannavo A, Liccardo D, Koch WJ (2013) Targeting cardiac β-adrenergic signaling via GRK2 inhibition for heart failure therapy. Front Physiol 4:264

    PubMed  PubMed Central  Google Scholar 

  51. Barrese V, Taglialatela M (2013) New advances in beta-blocker therapy in heart failure. Front Physiol 4:323

    PubMed  PubMed Central  Google Scholar 

  52. Ferrara N, Komici K, Corbi G, Pagano G, Furgi G, Rengo C, Femminella GD, Leosco D, Bonaduce D (2014) β-Adrenergic receptor responsiveness in aging heart and clinical implications. Front Physiol 4:396

    PubMed  PubMed Central  Google Scholar 

  53. Rath G, Balligand J-L, Chantal D (2012) Vasodilatory mechanisms of beta receptor blockade. Curr Hypertens Rep 14(4):310–317

    CAS  PubMed  Google Scholar 

  54. Lymperopoulos A, Rengo G, Koch WJ (2007) Adrenal adrenoceptors in heart failure: fine-tuning cardiac stimulation. Trends Mol Med 13(12):503–511

    CAS  PubMed  Google Scholar 

  55. Xiang Y, Devic E, Kobilka B (2002) The PDZ binding motif of the β1 adrenergic receptor modulates receptor trafficking and signaling in cardiac myocytes. J Biol Chem 277(37):33783–33790

    CAS  PubMed  Google Scholar 

  56. Zaugg M, Schaub MC (2008) β3-adrenergic receptor subtype signaling in senescent heart nitric oxide intoxication or “endogenous” β blockade for protection? Anesthesiology: The Journal of the American Society of Anesthesiologists, 109(6):956–959

    PubMed  Google Scholar 

  57. Gao Z-G, Jacobson KA (2017) Purinergic signaling in mast cell degranulation and asthma. Front Pharmacol 8:947

    PubMed  PubMed Central  Google Scholar 

  58. Zhang W, Yano N, Deng M, Mao Q, Shaw SK, Tseng Y-T (2011) β-Adrenergic receptor-PI3K signaling crosstalk in mouse heart: elucidation of immediate downstream signaling cascades. PLoS One 6(10):e26581

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Liggett SB (2001) β-Adrenergic receptors in the failing heart: the good, the bad, and the unknown. J Clin Invest 107(8):947–948

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Lymperopoulos A, Negussie S (2013) βArrestins in cardiac G protein-coupled receptor signaling and function: partners in crime or “good cop, bad cop”? Int J Mol Sci 14(12):24726–24741

    PubMed  PubMed Central  Google Scholar 

  61. Cannavo A, Koch WJ (2017) Targeting β3-adrenergic receptors in the heart: selective agonism and β-blockade. J Cardiovasc Pharmacol 69(2):71–78

    CAS  PubMed  Google Scholar 

  62. Penela P, Murga C, Ribas C, Tutor AS, Peregrín S, Mayor F Jr (2006) Mechanisms of regulation of G protein-coupled receptor kinases (GRKs) and cardiovascular disease. Cardiovasc Res 69(1):46–56

    CAS  PubMed  Google Scholar 

  63. Kaufman BD, Shaddy RE (2007) Beta-adrenergic receptor blockade and pediatric dilated cardiomyopathy. Prog Pediatr Cardiol 24(1):51–57

    Google Scholar 

  64. Bernstein D (2018) Cardiovascular receptors and signaling in heart failure. In: Heart Failure in the Child and Young Adult. Elsevier, pp 21–31.

  65. Rosmond R, Ukkola O, Chagnon M, Bouchard C, Björntorp P (2000) Polymorphisms of the β2-adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men. J Intern Med 248(3):239–244

    CAS  PubMed  Google Scholar 

  66. Richter W, Day P, Agrawal R, Bruss MD, Granier S, Wang YL, Rasmussen SG, Horner K, Wang P, Lei T (2008) Signaling from β1-and β2-adrenergic receptors is defined by differential interactions with PDE4. EMBO J 27(2):384–393

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Bristow MR (2000) β-Adrenergic receptor blockade in chronic heart failure. Circulation 101(5):558–569

    CAS  PubMed  Google Scholar 

  68. Lohse MJ, Engelhardt S, Eschenhagen T (2003) What is the role of β-adrenergic signaling in heart failure? Circ Res 93(10):896–906

    CAS  PubMed  Google Scholar 

  69. Bristow M, Hershberger R, Port JD, Minobe W, Rasmussen R (1989) Beta 1-and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol 35(3):295–303

    CAS  PubMed  Google Scholar 

  70. Makaritsis K, Triposkiadis F (2015) Beta adrenergic receptors. In: Introduction to translational cardiovascular research. Springer, pp 73–89.

  71. Kamal FA, Smrcka AV, Blaxall BC (2011) Taking the heart failure battle inside the cell: small molecule targeting of Gβγ subunits. J Mol Cell Cardiol 51(4):462–467

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Zhang P, Mende U (2011) Regulators of G-protein signaling in the heart and their potential as therapeutic targets. Circ Res 109(3):320–333

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Ciccarelli M, Santulli G, Pascale V, Trimarco B, Iaccarino G (2013) Adrenergic receptors and metabolism: role in development of cardiovascular disease. Front Physiol 4:265

    PubMed  PubMed Central  Google Scholar 

  74. Zhang Y, Matkovich SJ, Duan X, Gold JI, Koch WJ, Dorn GW II (2011) Nuclear effects of G-protein receptor kinase 5 on histone deacetylase 5–regulated gene transcription in heart failure. Gene Expr 4:659–668

    CAS  Google Scholar 

  75. Ho D, Yan L, Iwatsubo K, Vatner DE, Vatner SF (2010) Modulation of β-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5. Heart Fail Rev 15(5):495–512

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Métayé T, Gibelin H, Perdrisot R, Kraimps J-L (2005) Pathophysiological roles of G-protein-coupled receptor kinases. Cell Signal 17(8):917–928

    PubMed  Google Scholar 

  77. Grisanti LA, Schumacher SM, Tilley DG, Koch WJ (2018) Designer approaches for G protein–coupled receptor modulation for cardiovascular disease. JACC Basic Transl Sci 3(4):550–562

    PubMed  PubMed Central  Google Scholar 

  78. Franco A, Zhang L, Matkovich SJ, Kovacs A, Dorn GW II (2018) G-protein receptor kinases 2, 5 and 6 redundantly modulate smoothened-GATA transcriptional crosstalk in fetal mouse hearts. J Mol Cell Cardiol 121:60–68

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Belmonte SL, Blaxall BC (2011) G protein coupled receptor kinases as therapeutic targets in cardiovascular disease. Circ Res 109(3):309–319

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Elorza A, Penela P, Sarnago S, Mayor F (2003) MAPK-dependent degradation of G protein-coupled receptor kinase 2. J Biol Chem 278(31):29164–29173

    CAS  PubMed  Google Scholar 

  81. Nediani C, Formigli L, Perna A, Ibba-Manneschi L, Zecchi-Orlandini S, Fiorillo C, Ponziani V, Cecchi C, Liguori P, Fratini G (2000) Early changes induced in the left ventricle by pressure overload. An experimental study on swine heart. J Mol Cell Cardiol 32(1):131–142

    CAS  PubMed  Google Scholar 

  82. Pfleger JM, Gross P, Johnson J, Gao E, Houser SR, Koch WJ (2018) G protein-coupled receptor kinase 2 impairs fatty acid metabolism in the failing heart through novel mechanisms. J Mol Cell Cardiol 124:100

    Google Scholar 

  83. Chen M, Sato PY, Chuprun JK, Peroutka RJ, Otis NJ, Ibetti J, Pan S, Sheu S–S, Gao E, Koch WJ (2013) Pro-death signaling of GRK2 in cardiac myocytes after ischemic stress occurs via ERK-dependent, Hsp90–mediated mitochondrial targeting. Circ Res. 112(8): 1121–1134

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Walker J, Penn R, Hanania N, Dickey B, Bond R (2011) New perspectives regarding β2-adrenoceptor ligands in the treatment of asthma. Br J Pharmacol 163(1):18–28

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Selvam B, Wereszczynski J, Tikhonova IG (2012) Comparison of dynamics of extracellular accesses to the β1 and β2 adrenoceptors binding sites uncovers the potential of kinetic basis of antagonist selectivity. Chem Biol Drug Des 80(2):215–226

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Swaminath G, Lee TW, Kobilka B (2003) Identification of an allosteric binding site for Zn2+ on the β2 adrenergic receptor. J Biol Chem 278(1):352–356

    CAS  PubMed  Google Scholar 

  87. Freddolino PL, Kalani MYS, Vaidehi N, Floriano WB, Hall SE, Trabanino RJ, Kam VWT, Goddard WA (2004) Predicted 3D structure for the human β2 adrenergic receptor and its binding site for agonists and antagonists. Proc Natl Acad Sci 101(9):2736–2741

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Chan HS, Filipek S, Yuan S (2016) The principles of ligand specificity on beta-2-adrenergic receptor. Sci Rep 6:34736

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Hatton R, Cvjeticanin A, Lymperopoulos A (2015) The adrenergic system of the adrenal glands as a remote control of cardiac function. J Cardiovasc Dis 5:394–397

    Google Scholar 

  90. Swaminath G, Deupi X, Lee TW, Zhu W, Thian FS, Kobilka TS, Kobilka B (2005) Probing the β2 adrenoceptor binding site with catechol reveals differences in binding and activation by agonists and partial agonists. J Biol Chem 280(23):22165–22171

    CAS  PubMed  Google Scholar 

  91. Volovyk ZM, Wolf MJ, Prasad SVN, Rockman HA (2006) Agonist-stimulated β-adrenergic receptor internalization requires dynamic cytoskeletal actin turnover. J Biol Chem 281:9773–9780

    CAS  PubMed  Google Scholar 

  92. Tsuda T, Takefuji M, Wettschureck N, Kotani K, Morimoto R, Okumura T, Kaur H, Eguchi S, Sakaguchi T, Ishihama S (2017) Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction. J Exp Med 214(7):1877–1888

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Sato M (2013) Roles of accessory proteins for heterotrimeric G-protein in the development of cardiovascular diseases. Circ J 77(10):2455–2461

    CAS  PubMed  Google Scholar 

  94. Hernandez AF, Hammill BG, O’Connor CM, Schulman KA, Curtis LH, Fonarow GC (2009) Clinical effectiveness of beta-blockers in heart failure: findings from the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) Registry. J Am Coll Cardiol 53(2):184–192

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Albouaini K, Andron M, Alahmar A, Egred M (2007) Beta-blockers use in patients with chronic obstructive pulmonary disease and concomitant cardiovascular conditions. Int J Chron Obstruct Pulmon Dis 2(4):535–540

    PubMed  PubMed Central  Google Scholar 

  96. Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ (2003) Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 362(9377):7–13

    CAS  PubMed  Google Scholar 

  97. Kang M, Chung KY, Walker JW (2007) G-protein coupled receptor signaling in myocardium: not for the faint of heart. Physiology 22(3):174–184

    CAS  PubMed  Google Scholar 

  98. Liggett SB, Cresci S, Kelly RJ, Syed FM, Matkovich SJ, Hahn HS, Diwan A, Martini JS, Sparks L, Parekh RR (2008) A GRK5 polymorphism that inhibits β-adrenergic receptor signaling is protective in heart failure. Nat Med 14(5):510–517

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Petrie MC, Padmanabhan N, McDonald JE, Hillier C, Connell JM, McMurray JJ (2001) Angiotensin converting enzyme (ACE) and non-ACE dependent angiotensin II generation in resistance arteries from patients with heart failure and coronary heart disease. J Am Coll Cardiol 37(4):1056–1061

    CAS  PubMed  Google Scholar 

  100. Hawkins NM, Petrie MC, Jhund PS, Chalmers GW, Dunn FG, McMurray JJ (2009) Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology. Eur J Heart Fail 11(2):130–139

    PubMed  PubMed Central  Google Scholar 

  101. Rutten FH, Cramer MJM, Lammers JWJ, Grobbee DE, Hoes AW (2006) Heart failure and chronic obstructive pulmonary disease: an ignored combination? Eur J Heart Fail 8(7):706–711

    PubMed  Google Scholar 

  102. Gattis WA, O’Connor CM, Gallup DS, Hasselblad V, Gheorghiade M (2004) Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure: results of the Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial. J Am Coll Cardiol 43(9):1534–1541

    CAS  PubMed  Google Scholar 

  103. Lindholm LH, Carlberg B, Samuelsson O (2005) Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 366(9496):1545–1553

    CAS  PubMed  Google Scholar 

  104. Pose-Reino A, Pena-Seijo M (2007) Should beta-blockers remain first choice in the treatment of primary hypertension? Med Clin 129(19):733–735

    Google Scholar 

Download references

Acknowledgments

We are very grateful to Ali Ozoemena for his unalloyed pieces of advice to complete this article. We are thankful to Chinese Scholarship Council (CSC) for funding our research scholar FATIMA Majeed in her doctorate studies. Furthermore, all the authors of the manuscript also thank and acknowledge their respective Universities and Institutes.

Funding

The Qinghai Science and Technology Department Project (Nos. 2018-ZJ-730 & 2019-SF-134) supported this work.

Author information

Authors and Affiliations

  1. Department of Microbiological and Biochemical Pharmacy, School of Life Science, China Pharmaceutical University, Nanjing, 210009, Jiangsu Province, People’s Republic of China

    Daniel Chikere Ali

  2. Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, 211166, Nanjing, Jiangsu Province, People’s Republic of China

    Muhammad Naveed

  3. Department of Pharmacognosy, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu Province, People’s Republic of China

    Andrew Gordon

  4. Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, People’s Republic of China

    Fatima Majeed

  5. Faculty of Animal Production and Technology, The Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 6300, Punjab Province, Pakistan

    Muhammad Saeed

  6. Department of Pharmacy, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People’s Republic of China

    Michael I. Ogbuke

  7. Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, 63100, Punjab Province, Pakistan

    Muhammad Atif

  8. Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, People’s Republic of China

    Hafiz Muhammad Zubair

  9. Department of Human Anatomy, Medical College of Qinghai University, Xining, 810000, Qinghai Province, People’s Republic of China

    Li Changxing

Authors
  1. Daniel Chikere Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muhammad Naveed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew Gordon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fatima Majeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Muhammad Saeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael I. Ogbuke
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Muhammad Atif
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hafiz Muhammad Zubair
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Li Changxing
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Li Changxing.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ali, D.C., Naveed, M., Gordon, A. et al. β-Adrenergic receptor, an essential target in cardiovascular diseases. Heart Fail Rev 25, 343–354 (2020). https://doi.org/10.1007/s10741-019-09825-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-019-09825-x

Keywords

Search

Navigation