Skip to main content
SpringerLink
Log in

Role of β-Adrenoceptor/Adenylyl Cyclase System in Cardiac Hypertrophy

  • Chapter
  • First Online:
Cardiac Adaptations

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 4))

  • 1818 Accesses

Abstract

Activation of the sympathetic nervous system (SNS) releases norepinephrine, stimulates β-adrenoceptors, and plays a crucial role in the development of cardiac hypertrophy upon activation of various cellular signaling pathways in the heart. At early stages, norepinephrine-induced cardiac hypertrophy serves as an adaptive mechanism for maintaining heart function whereas at late stages, it is associated with contractile dysfunction, alterations in electrical activity, and programmed cell death. Activation of G s -protein coupled β 1- or β 2-adrenoceptors produces an increase in cardiac contractility and some deleterious effects whereas that of G i -protein coupled β 2- or β 3-adrenoceptors is known to result in beneficial adaptive actions in the heart. While the increase in G s -protein involves the downstream activation of adenylyl cyclase (AC), the activation of G i -proteins is associated with either a depression in AC or augmentation of guanylate cyclase activity. In this article, we discuss the physiological aspects of β-adrenergic signaling pathways and their modification in the hypertrophied heart as well as their participation in the transition of cardiac hypertrophy to heart failure. Furthermore, we highlight the actions of some components of the β-adrenoreceptor signaling cascade that may participate in the genesis of cardiac hypertrophy and thus serve as pharmacological targets for the prevention of cardiac hypertrophy or treatment of the hypertrophied failing heart.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Dhalla NS, Heyliger CE, Beamish RE, Innes IR (1987) Pathophysiological aspects of myocardial hypertrophy. Can J Cardiol 3:183–196

    PubMed  CAS  Google Scholar 

  2. Chien KR, Knowlton KU, Zhu H, Chien S (1997) Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response. FASEB J 5:3037–3046

    Google Scholar 

  3. Izumo S, Nadal-Ginard B, Mahdavi V (1988) Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci USA 85:339–343

    Article  PubMed  CAS  Google Scholar 

  4. Rockman HA, Ross RS, Harris AN et al (1991) Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc Natl Acad Sci USA 88:8277–8281

    Article  PubMed  CAS  Google Scholar 

  5. Laks MN (1976) Norepinephrine—the myocardial hypertrophy hormone? Am Heart J 94:674–675

    Article  Google Scholar 

  6. Ganguly PK, Lee SL, Beamish RE, Dhalla NS (1989) Altered sympathetic system and adrenoceptors during the development of cardiac hypertrophy. Am Heart J 118:520–525

    Article  PubMed  CAS  Google Scholar 

  7. Grossman W, Jones D, McLaurin LP (1975) Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 56:56–64

    Article  PubMed  CAS  Google Scholar 

  8. Meerson FZ, Kapelko VI (1965) The effect of cardiac hyperfunction on its automaticity and reactivity to the chronotropic effect of the vagus. Cor Vasa 7:264–272

    PubMed  CAS  Google Scholar 

  9. Rouleau JL, Pitt B, Dhalla NS et al (2003) Canadian prospective randomized flosequinan longevity evaluation investigators. Prognostic importance of the oxidized product of catecholamines, adrenolutin, in patients with severe heart failure. Am Heart J 145:926–932

    Article  PubMed  CAS  Google Scholar 

  10. Gauthier C, Langin D, Balligand JL (2000) β 3-adrenoceptors in the cardiovascular system. Trends Pharmacol Sci 21:426–431

    Article  PubMed  CAS  Google Scholar 

  11. Gauthier C, Leblais V, Kobzik L et al (1998) The negative inotropic effect of β 3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. J Clin Invest 102:137784

    Article  Google Scholar 

  12. Steinberg SF (2004) β 2-adrenergic receptor Signalling complexes in cardiomyocyte caveolae/lipid rafts. J Mol Cell Cardiol 37:407–415

    Article  PubMed  CAS  Google Scholar 

  13. Okamoto T, Murayama Y, Hayashi Y et al (1991) Identification of a Gs activator region of the β 2-adrenergic receptor that is autoregulated via protein kinase A-dependent phosphorylation. Cell 15:723–730

    Article  Google Scholar 

  14. Daaka Y, Luttrell LM, Lefkowitz RJ (1997) Switching of the coupling of the β 2-adrenergic receptor to different G proteins by protein kinase A. Nature 390:88–91

    Article  PubMed  CAS  Google Scholar 

  15. Ait-Mamar B, Cailleret M, Rucker-Martin C et al (2005) The cytosolic phospholipase A2 pathway, a safeguard of β 2-adrenergic cardiac effects in rat. J Biol Chem 280:1881–1890

    Article  CAS  Google Scholar 

  16. Hall RA, Premont RT, Chow CW et al (1998) The β 2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. Nature 392:626–630

    Article  PubMed  CAS  Google Scholar 

  17. Varghese P, Harrison RW, Lofthouse RA et al (2000) β 3-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility. J Clin Invest 106:697–703

    Article  PubMed  CAS  Google Scholar 

  18. Cheng HJ, Zhang ZS, Onishi K et al (2001) Upregulation of functional β 3-adrenergic receptor in the failing canine myocardium. Circ Res 89:599–606

    Article  PubMed  CAS  Google Scholar 

  19. D’Angelo DD, Sakata Y, Lorenz JN et al (1997) Transgenic Gαq overexpression induces cardiac contractile failure in mice. Proc Natl Acad Sci USA 94:8121–8126

    Article  PubMed  Google Scholar 

  20. Rogers JH, Tamirisa P, Kovacs A et al (1999) RGS4 causes increased mortality and reduced cardiac hypertrophy in response to pressure overload. J Clin Invest 104:567–576

    Article  PubMed  CAS  Google Scholar 

  21. Dorn GW 2nd, Tepe NM, Lorenz JN et al (1999) Low- and high-level transgenic expression of β 2-adrenergic receptors differentially affect cardiac hypertrophy and function in Gαq-overexpressing mice. Proc Natl Acad Sci USA 96:6400–6405

    Article  PubMed  CAS  Google Scholar 

  22. Liggett SB, Tepe NM, Lorenz JN et al (2000) Early and delayed consequences of β 2-adrenergic receptor overexpression in mouse hearts: critical role for expression level. Circulation 101:1707–1714

    Article  PubMed  CAS  Google Scholar 

  23. Bristow MR, Hershberger RE, Port JD et al (1989) β 1- and β 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol 35:295–303

    PubMed  CAS  Google Scholar 

  24. Marzo KP, Frey MJ, Wilson JR et al (1991) β-adrenergic receptor-G protein-adenylate cyclase complex in experimental canine congestive heart failure produced by rapid ventricular pacing. Circ Res 69:1546–1556

    Article  PubMed  CAS  Google Scholar 

  25. Dent MR, Tappia PS, Dhalla NS (2011) Gender differences in β-adrenoceptor system in cardiac hypertrophy due to arteriovenous fistula. J Cell Physiol 226:181–186

    Article  PubMed  CAS  Google Scholar 

  26. Farrukh HM, White M, Port JD et al (1993) Up-regulation of β 2-adrenergic receptors in previously transplanted, denervated nonfailing human hearts. J Am Coll Cardiol 22:1902–1908

    Article  PubMed  CAS  Google Scholar 

  27. The BEST Steering Committee (1995) Design of the β-blocker evaluation survival trial (BEST). Am J Cardiol 75:1220–1223

    Google Scholar 

  28. Engelhardt S, Hein L, Wiesmann F, Lohse MJ (1999) Progressive hypertrophy and heart failure in beta1-adrenergic receptor transgenic mice. Proc Natl Acad Sci USA 96:7059–7064

    Article  PubMed  CAS  Google Scholar 

  29. Milano CA, Allen LF, Rockman HA et al (1994) Enhanced myocardial function in transgenic mice overexpressing the β 2-adrenergic receptor. Science 264:582–586

    Article  PubMed  CAS  Google Scholar 

  30. Lefkowitz RJ, Rockman HA, Koch WJ (2000) Catecholamines, cardiac β-adrenergic receptors, and heart failure. Circulation 101:1634–1637

    Article  PubMed  CAS  Google Scholar 

  31. Tevaearai HT, Koch WJ (2004) Molecular restoration of β-adrenergic receptor Signalling improves contractile function of failing hearts. Trends Cardiovasc Med 14:252–256

    Article  PubMed  CAS  Google Scholar 

  32. Rohrer DK (1998) Physiological consequences of β-adrenergic receptor disruption. J Mol Med 76:764–772

    Article  PubMed  CAS  Google Scholar 

  33. Chruscinski AJ, Rohrer DK, Schauble E et al (1999) Targeted disruption of the β 2-adrenergic receptor gene. J Biol Chem 274:16694–16700

    Article  PubMed  CAS  Google Scholar 

  34. Iwaki K, Sukhatme VP, Shubeita HE, Chien KR (1990) α- and β-adrenergic stimulation induces distinct patterns of immediate early gene expression in neonatal rat myocardial cells. Fos/jun expression is associated with sarcomere assembly; Egr-1 induction is primarily an α 1-mediated response. J Biol Chem 265:13809–13817

    PubMed  CAS  Google Scholar 

  35. Dubus I, Samuel JL, Marotte F et al (1990) β-adrenergic agonists stimulate the synthesis of noncontractile but not contractile proteins in cultured myocytes isolated from adult rat heart. Circ Res 66:867–874

    Article  PubMed  CAS  Google Scholar 

  36. Ramirez MT, Zhao XL, Schulman H, Brown JH (1997) The nuclear δB isoform of Ca2+/calmodulin-dependent protein kinase II regulates atrial natriuretic factor gene expression in ventricular myocytes. J Biol Chem 272:31203–31208

    Article  PubMed  CAS  Google Scholar 

  37. McDonough PM, Hanford DS, Sprenkle AB et al (1997) Collaborative roles for c-Jun N-terminal kinase, c-Jun, serum response factor, and Sp1 in calcium-regulated myocardial gene expression. J Biol Chem 272:24046–24053

    Article  PubMed  CAS  Google Scholar 

  38. Schäfer M, Frischkopf K, Taimor G et al (2000) Hypertrophic effect of selective β 1-adrenoceptor stimulation on ventricular cardiomyocytes from adult rat. Am J Physiol Cell Physiol 279:C495–C503

    PubMed  Google Scholar 

  39. Morisco C, Zebrowski D, Condorelli G et al (2000) The Akt-glycogen synthase kinase 3β pathway regulates transcription of atrial natriuretic factor induced by β-adrenergic receptor stimulation in cardiac myocytes. J Biol Chem 275:14466–14475

    Article  PubMed  CAS  Google Scholar 

  40. Communal C, Singh K, Sawyer DB, Colucci WS (1999) Opposing effects of β 1- and β 2-adrenergic receptors on cardiac myocyte apoptosis: role of a pertussis toxin-sensitive G protein. Circulation 100:2210–2212

    Article  PubMed  CAS  Google Scholar 

  41. Zaugg M, Xu W, Lucchinetti E et al (2000) β-adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes. Circulation 102:344–350

    Article  PubMed  CAS  Google Scholar 

  42. Chesley A, Lundberg MS, Asai T et al (2000) The β 2-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G i -dependent coupling to phosphatidylinositol 3′-kinase. Circ Res 87:1172–1179

    Article  PubMed  CAS  Google Scholar 

  43. Zhu WZ, Wang SQ, Chakir K et al (2003) Linkage of β 1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/calmodulin kinase II. J Clin Invest 111:617–625

    PubMed  CAS  Google Scholar 

  44. Colomer JM, Mao L, Rockman HA, Means AR (2003) Pressure overload selectively up-regulates Ca2+/calmodulin-dependent protein kinase II in vivo. Mol Endocrinol 17:183–192

    Article  PubMed  CAS  Google Scholar 

  45. Luo J, McMullen JR, Sobkiw CL et al (2005) Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy. Mol Cell Biol 25:9491–9502

    Article  PubMed  CAS  Google Scholar 

  46. Nagoshi T, Matsui T, Aoyama T et al (2005) PI3 K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. J Clin Invest 115:2128–2138

    Article  PubMed  CAS  Google Scholar 

  47. Zhu WZ, Chakir K, Zhang S et al (2005) Heterodimerization of β 1- and β 2-adrenergic receptor subtypes optimizes β-adrenergic modulation of cardiac contractility. Circ Res 97:244–251

    Article  PubMed  CAS  Google Scholar 

  48. Breit A, Lagacé M, Bouvier M (2004) Hetero-oligomerization between β 2- and β 3-adrenergic receptors generates a β-adrenergic Signalling unit with distinct functional properties. J Biol Chem 279:28756–28765

    Article  PubMed  CAS  Google Scholar 

  49. Slotkin TA, Auman JT, Seidler FJ (2003) Ontogenesis of β-adrenoceptor Signalling: implications for perinatal physiology and for fetal effects of tocolytic drugs. J Pharmacol Exp Ther 306:1–7

    Article  PubMed  CAS  Google Scholar 

  50. Maurice DH, Palmer D, Tilley DG et al (2003) Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system. Mol Pharmacol 64:533–546

    Article  PubMed  CAS  Google Scholar 

  51. Choi DJ, Koch WJ, Hunter JJ, Rockman HA (1997) Mechanism of β-adrenergic receptor desensitization in cardiac hypertrophy is increased β-adrenergic receptor kinase. J Biol Chem 272:17223–17229

    Article  PubMed  CAS  Google Scholar 

  52. Lefkowitz RJ, Shenoy SK (2005) Transduction of receptor signals by β-arrestins. Science 308:512–517

    Article  PubMed  CAS  Google Scholar 

  53. Karliner JS, Simpson PC, Honbo N, Woloszyn W (1986) Mechanisms and time course of β 1 adrenoceptor desensitisation in mammalian cardiac myocytes. Cardiovasc Res 20:221–228

    Article  PubMed  CAS  Google Scholar 

  54. Iaccarino G, Tomhave ED, Lefkowitz RJ, Koch WJ (1998) Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by β-adrenergic receptor stimulation and blockade. Circulation 98:1783–1789

    Article  PubMed  CAS  Google Scholar 

  55. Chang HY, Klein RM, Kunos G (1982) Selective desensitization of cardiac β adrenoceptors by prolonged in vivo infusion of catecholamines in rats. J Pharmacol Exp Ther 221:784–789

    PubMed  CAS  Google Scholar 

  56. Elfellah MS, Reid JL (1990) Regulation of β-adrenoceptors in the guinea pig left ventricle and skeletal muscle following chronic agonist treatment. Eur J Pharmacol 182:387–392

    Article  PubMed  CAS  Google Scholar 

  57. Kudej RK, Iwase M, Uechi M et al (1997) Effects of chronic β-adrenergic receptor stimulation in mice. J Mol Cell Cardiol 29:2735–2746

    Article  PubMed  CAS  Google Scholar 

  58. Eschenhagen T, Mende U, Diederich M et al (1992) Long term β-adrenoceptor-mediated up-regulation of G i α and G o α mRNA levels and pertussis toxin-sensitive guanine nucleotide-binding proteins in rat heart. Mol Pharmacol 42:773–783

    PubMed  CAS  Google Scholar 

  59. Müller FU, Boheler KR, Eschenhagen T et al (1993) Isoprenaline stimulates gene transcription of the inhibitory G protein α-subunit G i α − 2 in rat heart. Circ Res 72:696–700

    Article  PubMed  Google Scholar 

  60. Reithmann C, Gierschik P, Sidiropoulos D et al (1989) Mechanism of noradrenaline-induced heterologous desensitization of adenylate cyclase stimulation in rat heart muscle cells: increase in the level of inhibitory G-protein α-subunits. Eur J Pharmacol 172:211–221

    Article  PubMed  CAS  Google Scholar 

  61. Bond RA, Lefkowitz RJ (1996) The third β is not the charm. J Clin Invest 98:241

    Article  PubMed  CAS  Google Scholar 

  62. Müller FU, Bokník P, Horst A et al (1995) In vivo isoproterenol treatment leads to downregulation of the mRNA encoding the cAMP response element binding protein in the rat heart. Biochem Biophys Res Commun 215:1043–1049

    Article  PubMed  Google Scholar 

  63. Kizaki K, Momozaki M, Akatsuka K et al (2004) Impaired gene expression of β 1-adrenergic receptor, but not stimulatory G-protein G s α, in rat ventricular myocardium treated with isoproterenol. Biol Pharm Bull 27:1130–1132

    Article  PubMed  CAS  Google Scholar 

  64. Vatner DE, Vatner SF, Nejima J et al (1989) Chronic norepinephrine elicits desensitization by uncoupling the beta-receptor. J Clin Invest 84:1741–1748

    Article  PubMed  CAS  Google Scholar 

  65. Perrino C, Naga Prasad SV et al (2005) Restoration of β-adrenergic receptor Signalling and contractile function in heart failure by disruption of the βARK1/phosphoinositide 3-kinase complex. Circulation 111:2579–2587

    Article  PubMed  CAS  Google Scholar 

  66. Sethi R, Saini HK, Guo X et al (2007) Dependence of changes in β-adrenoceptor signal transduction on type and stage of cardiac hypertrophy. J Appl Physiol 102:978–984

    Article  PubMed  CAS  Google Scholar 

  67. Bristow MR, Ginsburg R, Umans V et al (1986) β 1- and β 2-adrenergic-receptor subpopulations in non failing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective β 1-receptor down-regulation in heart failure. Circ Res 59:297–309

    Article  PubMed  CAS  Google Scholar 

  68. Bristow MR, Minobe WA, Raynolds MV et al (1993) Reduced β 1 receptor messenger RNA abundance in the failing human heart. J Clin Invest 92:2737–2745

    Article  PubMed  CAS  Google Scholar 

  69. Ungerer M, Böhm M, Elce JS (1993) Altered expression of β-adrenergic receptor kinase and β 1-adrenergic receptors in the failing human heart. Circulation 87:454–463

    Article  PubMed  CAS  Google Scholar 

  70. Tappia PS, Hata T, Hozaima MS et al (2001) Role of oxidative stress in catecholamine-induced changes in cardiac sarcolemmal Ca2+ transport. Arch Biochem Biophys 387:85–92

    Article  PubMed  CAS  Google Scholar 

  71. Wallukat G (2002) The -adrenergic receptors. Herz 27:683–690

    Article  PubMed  Google Scholar 

  72. Iaccarino G, Keys JR, Rapacciuolo A et al (2001) Regulation of myocardial βARK1 expression in catecholamine-induced cardiac hypertrophy in transgenic mice overexpressing α 1B-adrenergic receptors. J Am Coll Cardiol 38:534–540

    Article  PubMed  CAS  Google Scholar 

  73. D’Errico S, Neri M, Nieddu A et al (2011) Cardiac 1-adrenoceptor expression in two stress-induced cardiomyopathy-related deaths. Forensic Sci Int 207:e8–e11

    Article  PubMed  CAS  Google Scholar 

  74. Liggett SB, Wagoner LE, Craft LL et al (1998) The Ile164 β 2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 102:1534–1539

    Article  PubMed  CAS  Google Scholar 

  75. Green SA, Cole G, Jacinto M et al (1993) A polymorphism of the human β 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem 268:23116–23121

    PubMed  CAS  Google Scholar 

  76. Feldman AM, Jackson DG, Bristow MR et al (1991) Immuno detectable levels of the inhibitory guanine nucleotide-binding regulatory proteins in failing human heart: discordance with measurements of adenylate cyclase activity and levels of pertussis toxin substrate. J Mol Cell Cardiol 23:439–452

    Article  PubMed  CAS  Google Scholar 

  77. Ping P, Anzai T, Gao M, Hammond HK (1997) Adenylyl cyclase and G protein receptor kinase expression during development of heart failure. Am J Physiol 273:H707–H717

    PubMed  CAS  Google Scholar 

  78. Taussig R, Gilman AG (1995) Mammalian membrane-bound adenylyl cyclases. J Biol Chem 270:1–4

    Article  PubMed  CAS  Google Scholar 

  79. Ishikawa Y, Homcy CJ (1997) The adenylyl cyclases as integrators of transmembrane signal transduction. Circ Res 80:297–304

    Article  PubMed  CAS  Google Scholar 

  80. Tobise K, Ishikawa Y, Holmer SR et al (1994) Changes in type VI adenylyl cyclase isoform expression correlate with a decreased capacity for cAMP generation in the aging ventricle. Circ Res 74:596–603

    Article  PubMed  CAS  Google Scholar 

  81. Katsushika S, Chen L, Kawabe J et al (1992) Cloning and characterization of a sixth adenylyl cyclase isoform: types V and VI constitute a subgroup within the mammalian adenylyl cyclase family. Proc Natl Acad Sci USA 89:8774–8778

    Article  PubMed  CAS  Google Scholar 

  82. Cooper DM (1993) Inhibition of adenylate cyclase by Ca2+-a counterpart to stimulation by Ca2+/calmodulin. Biochem J 278:903–904

    Google Scholar 

  83. Gao T, Puri TS, Gerhardstein BL et al (1997) Identification and subcellular localization of the subunits of L-type calcium channels and adenylyl cyclase in cardiac myocytes. J Biol Chem 272:19401–19407

    Article  PubMed  CAS  Google Scholar 

  84. Chen Y, Harry A, Li J et al (1997) Adenylyl cyclase 6 is selectively regulated by protein kinase A phosphorylation in a region involved in Gα s stimulation. Proc Natl Acad Sci USA 94:14100–14104

    Article  PubMed  CAS  Google Scholar 

  85. Kawabe J, Ebina T, Toya Y et al (1996) Regulation of type V adenylyl cyclase by PMA-sensitive and -insensitive protein kinase C isoenzymes in intact cells. FEBS Lett 384:273–276

    Article  PubMed  CAS  Google Scholar 

  86. Espinasse I, Iourgenko V, Defer N et al (1995) Type V, but not type VI, adenylyl cyclase mRNA accumulates in the rat heart during ontogenic development. Correlation with increased global adenylyl cyclase activity. J Mol Cell Cardiol 27:1789–1795

    Article  PubMed  CAS  Google Scholar 

  87. Jourdan KB, Mason NA, Long L et al (2001) Characterization of adenylyl cyclase isoforms in rat peripheral pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 280:L1359–L1369

    PubMed  CAS  Google Scholar 

  88. Ishikawa Y, Sorota S, Kiuchi K et al (1994) Downregulation of adenylyl cyclase types V and VI mRNA levels in pacing-induced heart failure in dogs. J Clin Invest 93:2224–2229

    Article  PubMed  CAS  Google Scholar 

  89. Cooper DM (2003) Molecular and cellular requirements for the regulation of adenylate cyclases by calcium. Biochem Soc Trans 31:912–915

    Article  PubMed  CAS  Google Scholar 

  90. Gao MH, Lai NC, Roth DM et al (1999) Adenylyl cyclase increases responsiveness to catecholamine stimulation in transgenic mice. Circulation 99:1618–1622

    Article  PubMed  CAS  Google Scholar 

  91. Takahashi T, Tang T, Lai NC et al (2006) Increased cardiac adenylyl cyclase expression is associated with increased survival after myocardial infarction. Circulation 114:388–396

    Article  PubMed  CAS  Google Scholar 

  92. Sugano Y, Lai NC, Gao MH et al (2011) Activated expression of cardiac adenylyl cyclase 6 reduces dilation and dysfunction of the pressure-overloaded heart. Biochem Biophys Res Commun 405:349–355

    Article  PubMed  CAS  Google Scholar 

  93. Tang T, Gao MH, Lai NC et al (2008) Adenylyl cyclase type 6 deletion decreases left ventricular function via impaired calcium handling. Circulation 117:61–69

    Article  PubMed  CAS  Google Scholar 

  94. Hanoune J, Pouille Y, Tzavara E et al (1997) Adenylyl cyclases: structure, regulation and function in an enzyme superfamily. Mol Cell Endocrinol 128:179–194

    Article  PubMed  CAS  Google Scholar 

  95. Tepe NM, Lorenz JN, Yatani A et al (1999) Altering the receptor-effector ratio by transgenic overexpression of type V adenylyl cyclase: enhanced basal catalytic activity and function without increased cardiomyocyte β-adrenergic signalling. Biochemistry 38:16706–16713

    Article  PubMed  CAS  Google Scholar 

  96. Okumura S, Vatner DE, Kurotani R et al (2007) Disruption of type 5 adenylyl cyclase enhances desensitization of cyclic adenosine monophosphate signal and increases Akt signal with chronic catecholamine stress. Circulation 116:1776–1783

    Article  PubMed  CAS  Google Scholar 

  97. Ishikawa Y, Iwatsubo K, Tsunematsu T, Okumura S (2005) Genetic manipulation and functional analysis of cAMP signalling in cardiac muscle: implications for a new target of pharmacotherapy. Biochem Soc Trans 33:1337–1340

    Article  PubMed  CAS  Google Scholar 

  98. Okumura S, Takagi G, Kawabe J et al (2003) Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload. Proc Natl Acad Sci USA 100:9986–9990

    Article  PubMed  CAS  Google Scholar 

  99. Tang T, Lai NC, Roth DM et al (2006) Adenylyl cyclase type V deletion increases basal left ventricular function and reduces left ventricular contractile responsiveness to β-adrenergic stimulation. Basic Res Cardiol 101:117–126

    Article  PubMed  CAS  Google Scholar 

  100. Okumura S, Kawabe J, Yatani A et al (2003) Type 5 adenylyl cyclase disruption alters not only sympathetic but also parasympathetic and calcium-mediated cardiac regulation. Circ Res 93:364–371

    Article  PubMed  CAS  Google Scholar 

  101. Vatner SF, Yan L, Ishikawa Y et al (2009) Adenylyl cyclase type 5 disruption prolongs longevity and protects the heart against stress. Circ J 73:195–200

    Article  PubMed  CAS  Google Scholar 

  102. Yan L, Vatner DE, O’Connor JP et al (2007) Type 5 adenylyl cyclase disruption increases longevity and protects against stress. Cell 130:247–258

    Article  PubMed  CAS  Google Scholar 

  103. Yan L, Williams JG, Dillinger JG et al (2009) Type 5 adenylyl cyclase disruption enhances exercise capacity not due to improved cardiac output, but rather to resistance to oxidative stress in skeletal muscle. Circulation 120:S532

    Article  Google Scholar 

  104. Yan L, Dillinger JG, Williams JG et al (2009) Inhibition of Type 5 adenylyl cyclase rescues cardiomyopathy induced by overexpressed β 2-adrenergic receptors in the heart. Circulation 120:S1178

    Article  Google Scholar 

  105. Iwatsubo K, Minamisawa S, Tsunematsu T et al (2004) Direct inhibition of type 5 adenylyl cyclase prevents myocardial apoptosis without functional deterioration. J Biol Chem 279:40938–40945

    Article  PubMed  CAS  Google Scholar 

  106. Babich M, Atkinson J, Piascik MT (1985) The effects of trime to quinol on the intact rabbit heart and myocardial adenylate cyclase activity: evidence for spare myocardial β receptors. J Mol Cell Cardiol 17:565–574

    Article  PubMed  CAS  Google Scholar 

  107. Gaudin C, Ishikawa Y, Wight DC et al (1995) Overexpression of G s α protein in the hearts of transgenic mice. J Clin Invest 95:1676–1683

    Article  PubMed  CAS  Google Scholar 

  108. Antos CL, Frey N, Marx SO et al (2011) Dilated cardiomyopathy and sudden death resulting from constitutive activation of protein kinase A. Circ Res 89:997–1004

    Article  Google Scholar 

  109. Rottlaender D, Matthes J, Vatner SF et al (2007) Functional adenylyl cyclase inhibition in murine cardiomyocytes by 2′(3′)-O-(N-methylanthraniloyl)-guanosine 5′-[γ-thio]triphosphate. J Pharmacol Exp Ther 321:608–615

    Article  PubMed  CAS  Google Scholar 

  110. Levy DE, Bao M, Cherbavaz DB et al (2003) Metal coordination-based inhibitors of adenylyl cyclase: novel potent P-site antagonists. J Med Chem 46:2177–2186

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The research in this article was supported by a grant from the Canadian Institute of Health Research (CIHR) and Slovak Scientific Grant Agency (VEGA) 1/0638/12. The infrastructural support for this study was provided by the St. Boniface Hospital Research Foundation.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32, Bratislava, Slovak Republic

    Adriana Adameova

  2. Asper Clinical Research Institute, St. Boniface Hospital Research Centre, Winnipeg, Canada

    Paramjit S. Tappia

  3. Institute of Cardiovascular Sciences and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla

Authors
  1. Adriana Adameova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paramjit S. Tappia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naranjan S. Dhalla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adriana Adameova .

Editor information

Editors and Affiliations

  1. Czech Republic, Institute of Physiology, Academy of Sciences of the, Videnska 1083, Prague, 142 20, Czech Republic

    Bohuslav Ostadal

  2. St. Boniface General Hospital, Research Centre, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Adameova, A., Tappia, P.S., Dhalla, N.S. (2013). Role of β-Adrenoceptor/Adenylyl Cyclase System in Cardiac Hypertrophy. In: Ostadal, B., Dhalla, N. (eds) Cardiac Adaptations. Advances in Biochemistry in Health and Disease, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5203-4_16

Download citation

Publish with us

Policies and ethics

Search

Navigation