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Myocyte Adrenoceptor Signaling Pathways

Science, 6 June 2003
Vol. 300, Issue 5625, p. 1530-1532
DOI: 10.1126/science.1079206

Myocyte Adrenoceptor Signaling Pathways

  1. Yang Xiang,
  2. Brian K. Kobilka*
  1. Department of Molecular and Cellular Physiology, Stanford Medical Center, Palo Alto, CA 94305, USA.
  1. * To whom correspondence should be addressed: kobilka{at}


Adrenoceptors (ARs), members of the G protein–coupled receptor superfamily, form the interface between the sympathetic nervous system and the cardiovascular system, with integral roles in the rapid regulation of myocardial function. However, in heart failure, chronic catecholamine stimulation of adrenoceptors has been linked to pathologic cardiac remodeling, including myocyte apoptosis and hypertrophy. In cardiac myocytes, activation of AR subtypes results in coupling to different G proteins and induction of specific signaling pathways, which is partly regulated by the subtype-specific distribution of receptors in plasma membrane compartments containing distinct complexes of signaling molecules. The Connections Maps of the Adrenergic and Myocyte Adrenergic Signaling Pathways bring into focus the specific signaling pathways of individual AR subtypes and their relevant functions in vivo.


Y. Xiang and B. K. Kobilka, Myocyte Adrenoceptor Signaling Pathways. Science 300, 1530-1532 (2003).

Insulin Inhibits Cardiac Contractility by Inducing a Gi-Biased {beta}2-Adrenergic Signaling in Hearts
Q. Fu, B. Xu, Y. Liu, D. Parikh, J. Li, Y. Li, Y. Zhang, C. Riehle, Y. Zhu, T. Rawlings et al.
Diabetes 63, 2676-2689 (1 August 2014)

Paradoxical Effects on Force Generation after Efficient {beta}1-Adrenoceptor Knockdown in Reconstituted Heart Tissue
C. Neuber, O. J. Muller, F. C. Hansen, A. Eder, A. Witten, F. Ruhle, M. Stoll, H. A. Katus, T. Eschenhagen, A. El-Armouche et al.
J. Pharmacol. Exp. Ther. 349, 39-46 (1 April 2014)

Biochemistry of cardiomyopathy in the mitochondrial disease Friedreich's ataxia
D. J. R. Lane, M. L.-H. Huang, S. Ting, S. Sivagurunathan, and D. R. Richardson
Biochem. J. 453, 321-336 (1 August 2013)

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade
L. Bellocchio, E. Soria-Gomez, C. Quarta, M. Metna-Laurent, P. Cardinal, E. Binder, A. Cannich, A. Delamarre, M. Haring, M. Martin-Fontecha et al.
Proc. Natl. Acad. Sci. USA 110, 4786-4791 (19 March 2013)

Anchoring Proteins as Regulators of Signaling Pathways
A. Perino, A. Ghigo, J. D. Scott, and E. Hirsch
Circ. Res. 111, 482-492 (3 August 2012)

Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure ethiology and correlates to clinical variables
F. Monto, E. Oliver, D. Vicente, J. Rueda, J. Aguero, L. Almenar, M. D. Ivorra, D. Barettino, and P. D'Ocon
Am. J. Physiol. Heart Circ. Physiol. 303, H368-H376 (1 August 2012)

Selective {beta}2-Adrenoreceptor Stimulation Attenuates Myocardial Cell Death and Preserves Cardiac Function After Ischemia-Reperfusion Injury
S. Bhushan, K. Kondo, B. L. Predmore, M. Zlatopolsky, A. L. King, C. Pearce, H. Huang, Y.-X. Tao, M. E. Condit, D. J. Lefer et al.
Arterioscler. Thromb. Vasc. Bio. 32, 1865-1874 (1 August 2012)

Phosphodiesterases coordinate cAMP propagation induced by two stimulatory G protein-coupled receptors in hearts
S. Liu, Y. Li, S. Kim, Q. Fu, D. Parikh, B. Sridhar, Q. Shi, X. Zhang, Y. Guan, X. Chen et al.
Proc. Natl. Acad. Sci. USA 109, 6578-6583 (24 April 2012)

Phosphodiesterases and subcellular compartmentalized cAMP signaling in the cardiovascular system
A. Stangherlin, and M. Zaccolo
Am. J. Physiol. Heart Circ. Physiol. 302, H379-H390 (1 January 2012)

Phosphodiesterase type-2 and NO-dependent S-nitrosylation mediate the cardioinhibition of the antihypertensive catestatin
T. Angelone, A. M. Quintieri, T. Pasqua, S. Gentile, B. Tota, S. K. Mahata, and M. C. Cerra
Am. J. Physiol. Heart Circ. Physiol. 302, H431-H442 (1 January 2012)

Confinement of {beta}1- and {beta}2-adrenergic receptors in the plasma membrane of cardiomyocyte-like H9c2 cells is mediated by selective interactions with PDZ domain and A-kinase anchoring proteins but not caveolae
C. D. Valentine, and P. M. Haggie
Mol. Biol. Cell 22, 2970-2982 (15 August 2011)

Compartmentalization of {beta}-Adrenergic Signals in Cardiomyocytes
Y. K. Xiang, and P. M. Haggie
Circ. Res. 109, 231-244 (8 July 2011)

{beta}2-Adrenergic Receptor Lysosomal Trafficking Is Regulated by Ubiquitination of Lysyl Residues in Two Distinct Receptor Domains
K. Xiao, and S. K. Shenoy
J Biol Chem 286, 12785-12795 (8 April 2011)

Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies
N. J. Palpant, F. B. Bedada, B. Peacock, B. R. Blazar, J. M. Metzger, and J. Tolar
Am. J. Physiol. Heart Circ. Physiol. 300, H356-H365 (1 January 2011)

Regulation of Mammalian Autophagy in Physiology and Pathophysiology
B. Ravikumar, S. Sarkar, J. E. Davies, M. Futter, M. Garcia-Arencibia, Z. W. Green-Thompson, M. Jimenez-Sanchez, V. I. Korolchuk, M. Lichtenberg, S. Luo et al.
Physiol. Rev. 90, 1383-1435 (1 October 2010)

Sympathetic Stimulation of Adult Cardiomyocytes Requires Association of AKAP5 With a Subpopulation of L-Type Calcium Channels
C. B. Nichols, C. F. Rossow, M. F. Navedo, R. E. Westenbroek, W. A. Catterall, L. F. Santana, and G. S. McKnight
Circ. Res. 107, 747-756 (17 September 2010)

Equilibrium between Adenylyl Cyclase and Phosphodiesterase Patterns Adrenergic Agonist Dose-Dependent Spatiotemporal cAMP/Protein Kinase A Activities in Cardiomyocytes
V. De Arcangelis, S. Liu, D. Zhang, D. Soto, and Y. K. Xiang
Mol. Pharmacol. 78, 340-349 (1 September 2010)

Rapid Delivery of Internalized Signaling Receptors to the Somatodendritic Surface by Sequence-Specific Local Insertion
Y. J. Yu, R. Dhavan, M. W. Chevalier, G. A. Yudowski, and M. von Zastrow
J. Neurosci. 30, 11703-11714 (1 September 2010)

PKA phosphorylates histone deacetylase 5 and prevents its nuclear export, leading to the inhibition of gene transcription and cardiomyocyte hypertrophy
C. H. Ha, J. Y. Kim, J. Zhao, W. Wang, B. S. Jhun, C. Wong, and Z. G. Jin
Proc. Natl. Acad. Sci. USA 107, 15467-15472 (31 August 2010)

{beta}1-Adrenergic receptor activation induces mouse cardiac myocyte death through both L-type calcium channel-dependent and -independent pathways
W. Wang, H. Zhang, H. Gao, H. Kubo, R. M. Berretta, X. Chen, and S. R. Houser
Am. J. Physiol. Heart Circ. Physiol. 299, H322-H331 (1 August 2010)

Beyond Desensitization: Physiological Relevance of Arrestin-Dependent Signaling
L. M. Luttrell, D. Gesty-Palmer, and D. R. Sibley
Pharmacol. Rev. 62, 305-330 (1 June 2010)

{beta}2-Adrenergic Receptor Redistribution in Heart Failure Changes cAMP Compartmentation
V. O. Nikolaev, A. Moshkov, A. R. Lyon, M. Miragoli, P. Novak, H. Paur, M. J. Lohse, Y. E. Korchev, S. E. Harding, J. Gorelik et al.
Science 327, 1653-1657 (26 March 2010)

{beta}-Adrenergic signaling accelerates and synchronizes cardiac ryanodine receptor response to a single L-type Ca2+ channel
P. Zhou, Y.-T. Zhao, Y.-B. Guo, S.-M. Xu, S.-H. Bai, E. G. Lakatta, H. Cheng, X.-M. Hao, and S.-Q. Wang
Proc. Natl. Acad. Sci. USA 106, 18028-18033 (20 October 2009)

Loss of M2 muscarinic receptor function inhibits development of hypoxic bradycardia and alters cardiac {beta}-adrenergic sensitivity in larval zebrafish (Danio rerio)
S. L. Steele, K. H. A. Lo, V. W. T. Li, S. H. Cheng, M. Ekker, and S. F. Perry
Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R412-R420 (1 August 2009)

Cargo-Mediated Regulation of a Rapid Rab4-Dependent Recycling Pathway
G. A. Yudowski, M. A. Puthenveedu, A. G. Henry, and M. von Zastrow
Mol. Biol. Cell 20, 2774-2784 (1 June 2009)

Dynamic Protein Kinase A Activities Induced by {beta}-Adrenoceptors Dictate Signaling Propagation for Substrate Phosphorylation and Myocyte Contraction
D. Soto, V. De Arcangelis, J. Zhang, and Y. Xiang
Circ. Res. 104, 770-779 (27 March 2009)

Phosphodiesterase 4 and Phosphatase 2A Differentially Regulate cAMP/Protein Kinase A Signaling for Cardiac Myocyte Contraction under Stimulation of {beta}1 Adrenergic Receptor
V. De Arcangelis, D. Soto, and Y. Xiang
Mol. Pharmacol. 74, 1453-1462 (1 November 2008)

Signaling from {beta}1- and {beta}2-adrenergic receptors is defined by differential interactions with PDE4
W. Richter, P. Day, R. Agrawal, M. D. Bruss, S. Granier, Y. L. Wang, S. G. F. Rasmussen, K. Horner, P. Wang, T. Lei et al.
EMBO J. 27, 384-393 (23 January 2008)

{beta}-Cardiotoxin: a new three-finger toxin from Ophiophagus hannah (king cobra) venom with beta-blocker activity
N. Rajagopalan, Y. F. Pung, Y. Z. Zhu, P. T. H. Wong, P. P. Kumar, and R. M. Kini
FASEB J. 21, 3685-3695 (1 November 2007)

Organization of {beta}-adrenoceptor signaling compartments by sympathetic innervation of cardiac myocytes
O. G. Shcherbakova, C. M. Hurt, Y. Xiang, M. L. Dell'Acqua, Q. Zhang, R. W. Tsien, and B. K. Kobilka
JCB 176, 521-533 (12 February 2007)

Small Heat-Shock Protein Hsp20 Attenuates {beta}-Agonist-Mediated Cardiac Remodeling Through Apoptosis Signal-Regulating Kinase 1
G.-C. Fan, Q. Yuan, G. Song, Y. Wang, G. Chen, J. Qian, X. Zhou, Y. J. Lee, M. Ashraf, E. G. Kranias et al.
Circ. Res. 99, 1233-1242 (24 November 2006)

Differential Regulation of the Cell-Surface Targeting and Function of beta- and {alpha}1-Adrenergic Receptors by Rab1 GTPase in Cardiac Myocytes
C. M. Filipeanu, F. Zhou, E. K. Fugetta, and G. Wu
Mol. Pharmacol. 69, 1571-1578 (1 May 2006)

Enhancement of the Recycling and Activation of beta-Adrenergic Receptor by Rab4 GTPase in Cardiac Myocytes
C. M. Filipeanu, F. Zhou, M. L. Lam, K. E. Kerut, W. C. Claycomb, and G. Wu
J Biol Chem 281, 11097-11103 (21 April 2006)

beta-Arrestin-dependent, G Protein-independent ERK1/2 Activation by the beta2 Adrenergic Receptor
S. K. Shenoy, M. T. Drake, C. D. Nelson, D. A. Houtz, K. Xiao, S. Madabushi, E. Reiter, R. T. Premont, O. Lichtarge, R. J. Lefkowitz et al.
J Biol Chem 281, 1261-1273 (13 January 2006)

The Zinc Finger-Only Protein Zfp260 Is a Novel Cardiac Regulator and a Nuclear Effector of {alpha}1-Adrenergic Signaling
S. Debrus, L. Rahbani, M. Marttila, B. Delorme, P. Paradis, and M. Nemer
Mol. Cell. Biol. 25, 8669-8682 (1 October 2005)

Persistent Sympathetic Activation During Chronic Antihypertensive Therapy: A Potential Mechanism for Long Term Morbidity?
Q. Fu, R. Zhang, S. Witkowski, A. Arbab-Zadeh, A. Prasad, K. Okazaki, and B. D. Levine
Hypertension 45, 513-521 (1 April 2005)

cGMP Catabolism by Phosphodiesterase 5A Regulates Cardiac Adrenergic Stimulation by NOS3-Dependent Mechanism
E. Takimoto, H. C. Champion, D. Belardi, J. Moslehi, M. Mongillo, E. Mergia, D. C. Montrose, T. Isoda, K. Aufiero, M. Zaccolo et al.
Circ. Res. 96, 100-109 (7 January 2005)

Interaction with Cystic Fibrosis Transmembrane Conductance Regulator-associated Ligand (CAL) Inhibits {beta}1-Adrenergic Receptor Surface Expression
J. He, M. Bellini, J. Xu, A. M. Castleberry, and R. A. Hall
J Biol Chem 279, 50190-50196 (26 November 2004)

Occurrence of a tetrodotoxin-sensitive calcium current in rat ventricular myocytes after long-term myocardial infarction
J. L Alvarez, E. Salinas-Stefanon, G. Orta, T. Ferrer, K. Talavera, L. Galan, and G. Vassort
Cardiovasc Res 63, 653-661 (1 September 2004)

Cellular mechanisms in sympatho-modulation of the heart
M. Zaugg, and M. C. Schaub
Br J Anaesth 93, 34-52 (1 July 2004)

Hexosamine Pathway Is Responsible for Inhibition by Diabetes of Phenylephrine-Induced Inotropy
Y. Pang, P. Bounelis, J. C. Chatham, and R. B. Marchase
Diabetes 53, 1074-1081 (1 April 2004)

Balanced expression of mitochondrial apoptosis regulatory proteins correlates with long-term survival of cardiac allografts
T. C. Tung, G. Cui, K. Oshima, H. Laks, and L. Sen
Am. J. Physiol. Heart Circ. Physiol. 285, H2832-H2841 (1 December 2003)

Modeling {beta}-Adrenergic Control of Cardiac Myocyte Contractility in Silico
J. J. Saucerman, L. L. Brunton, A. P. Michailova, and A. D. McCulloch
J Biol Chem 278, 47997-48003 (28 November 2003)

Localization of Functional Endothelin Receptor Signaling Complexes in Cardiac Transverse Tubules
V. G. Robu, E. S. Pfeiffer, S. L. Robia, R. C. Balijepalli, Y. Pi, T. J. Kamp, and J. W. Walker
J Biol Chem 278, 48154-48161 (28 November 2003)

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