![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RP Xiao, X Ji and EG Lakatta
Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.
Recently we demonstrated that the effects of beta 2-adrenoceptor (AR) stimulation to augment Ca2+ current (ICa), cytosolic Ca2+ (Cai) transients, and contractility in rat ventricular myocytes are largely dissociated from its effect to increase cellular cAMP levels. This result suggested that beta 2ARs might be coupled to signaling pathways other than the Gs alpha-mediated activation of adenylyl cyclase. Here we show that pertussis toxin (PTX) pretreatment specifically potentiates the responses of rat heart cells to beta 2AR but not beta 1AR stimulation. After PTX pretreatment, 1) the dose-response curve for the effects of the beta 2AR agonist zinterol on contraction amplitude is shifted leftward and upward (EC50 changed from about 1.0 microM to 70 nM), 2) in indo-1-loaded cells, the maximal effects of zinterol (10(- 5) M) on Cai transient and contraction amplitudes are additionally increased 1.7- and 2.0-fold, respectively, over those in control cells, and 3) the increase in ICa amplitude induced by the same zinterol concentration is potentiated by 2.5-fold. Similar effects of PTX are observed when beta 2ARs are stimulated by isoproterenol in the presence of a selective beta 1AR blocker, CGP 20712A. All effects of beta 2AR agonists in both PTX-treated and control cells are abolished by a selective beta 2AR blocker, ICI 118,551. In contrast, neither the base- line ICa, Cai transient, and contraction in the absence of beta AR stimulation nor the beta 1AR-mediated augmentations of these parameters are significantly altered by PTX treatment. These results demonstrate, for the first time, that the Gs-coupled beta 2AR can simultaneously activate a pathway that leads to functional inhibition in cardiac cells via a PTX-sensitive G protein. The activation of more than one G protein during beta 2AR stimulation, leading to functionally opposite effects, may provide a mechanism to protect the heart from Ca2+ overload and arrhythmias during the response to stress.
This article has been cited by other articles:
|
|
 |
|
  K. Janssens, M. Boussemaere, S. Wagner, K. Kopka, and C. Denef {beta}1-Adrenoceptors in Rat Anterior Pituitary May Be Constitutively Active. Inverse Agonism of CGP 20712A on Basal 3',5'-Cyclic Adenosine 5'-Monophosphate Levels Endocrinology, May 1, 2008; 149(5): 2391 - 2402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Faucher, F. E. Gannier, J. M. Lignon, P. Cosnay, and C. O. Malecot Roles of PKA, PI3K, and cPLA2 in the NO-mediated negative inotropic effect of {beta}2-adrenoceptor agonists in guinea pig right papillary muscles Am J Physiol Cell Physiol, January 1, 2008; 294(1): C106 - C117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Hulme, R. E. Westenbroek, T. Scheuer, and W. A. Catterall Phosphorylation of serine 1928 in the distal C-terminal domain of cardiac CaV1.2 channels during beta1-adrenergic regulation PNAS, October 31, 2006; 103(44): 16574 - 16579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Queen, Y. Ji, B. Xu, L. Young, K. Yao, A. W. Wyatt, D. J. Rowlands, R. C. M. Siow, G. E. Mann, and A. Ferro Mechanisms underlying {beta}2-adrenoceptor-mediated nitric oxide generation by human umbilical vein endothelial cells J. Physiol., October 15, 2006; 576(2): 585 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. E. Schutzer, H. Xue, J. F. Reed, and S. L. Mader Effect of Age on Vascular {beta}2-Adrenergic Receptor Desensitization Is Not Mediated by the Receptor Coupling to G{alpha}i Proteins. J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2006; 61(9): 899 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Giembycz and R. Newton Beyond the dogma: novel {beta}2-adrenoceptor signalling in the airways. Eur. Respir. J., June 1, 2006; 27(6): 1286 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mittra and J.-P. Bourreau Gs and Gi coupling of adrenomedullin in adult rat ventricular myocytes Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1842 - H1847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Alessandri-Haber, O. A. Dina, E. K. Joseph, D. Reichling, and J. D. Levine A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators. J. Neurosci., April 5, 2006; 26(14): 3864 - 3874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Germack and J. M. Dickenson Induction of {beta}3-Adrenergic Receptor Functional Expression following Chronic Stimulation with Noradrenaline in Neonatal Rat Cardiomyocytes J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 392 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bernstein, G. Fajardo, M. Zhao, T. Urashima, J. Powers, G. Berry, and B. K. Kobilka Differential cardioprotective/cardiotoxic effects mediated by {beta}-adrenergic receptor subtypes Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2441 - H2449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wettschureck and S. Offermanns Mammalian G Proteins and Their Cell Type Specific Functions Physiol Rev, October 1, 2005; 85(4): 1159 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhu, X. Zeng, M. Zheng, and R.-P. Xiao The Enigma of {beta}2-Adrenergic Receptor Gi Signaling in the Heart: The Good, the Bad, and the Ugly Circ. Res., September 16, 2005; 97(6): 507 - 509. [Full Text] [PDF]
|
|
|
|
|
|
W.-Z. Zhu, K. Chakir, S. Zhang, D. Yang, C. Lavoie, M. Bouvier, T. E. Hebert, E. G. Lakatta, H. Cheng, and R.-P. Xiao Heterodimerization of {beta}1- and {beta}2-Adrenergic Receptor Subtypes Optimizes {beta}-Adrenergic Modulation of Cardiac Contractility Circ. Res., August 5, 2005; 97(3): 244 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Ait-Mamar, M. Cailleret, C. Rucker-Martin, A. Bouabdallah, G. Candiani, C. Adamy, P. Duvaldestin, F. Pecker, N. Defer, and C. Pavoine The Cytosolic Phospholipase A2 Pathway, a Safeguard of {beta}2-Adrenergic Cardiac Effects in Rat J. Biol. Chem., May 13, 2005; 280(19): 18881 - 18890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Robay, G. Toumaniantz, V. Leblais, and C. Gauthier Transfected {beta}3- but Not {beta}2-Adrenergic Receptors Regulate Cystic Fibrosis Transmembrane Conductance Regulator Activity via a New Pathway Involving the Mitogen-Activated Protein Kinases Extracellular Signal-Regulated Kinases Mol. Pharmacol., March 1, 2005; 67(3): 648 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gallego, R. Setien, L. Puebla, M. d. C. Boyano-Adanez, E. Arilla, and O. Casis {alpha}1-Adrenoceptors stimulate a G{alpha}s protein and reduce the transient outward K+ current via a cAMP/PKA-mediated pathway in the rat heart Am J Physiol Cell Physiol, March 1, 2005; 288(3): C577 - C585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Leblais, S.-H. Jo, K. Chakir, V. Maltsev, M. Zheng, M. T. Crow, W. Wang, E. G. Lakatta, and R.-P. Xiao Phosphatidylinositol 3-Kinase Offsets cAMP-Mediated Positive Inotropic Effect via Inhibiting Ca2+ Influx in Cardiomyocytes Circ. Res., December 10, 2004; 95(12): 1183 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, W. Zhu, S. Wang, D. Yang, M. T. Crow, R.-P. Xiao, and H. Cheng Sustained {beta}1-Adrenergic Stimulation Modulates Cardiac Contractility by Ca2+/Calmodulin Kinase Signaling Pathway Circ. Res., October 15, 2004; 95(8): 798 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Hoogland and P. Saggau Facilitation of L-Type Ca2+ Channels in Dendritic Spines by Activation of {beta}2 Adrenergic Receptors J. Neurosci., September 29, 2004; 24(39): 8416 - 8427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Ahmet, M. Krawczyk, P. Heller, C. Moon, E. G. Lakatta, and M. I. Talan Beneficial Effects of Chronic Pharmacological Manipulation of {beta}-Adrenoreceptor Subtype Signaling in Rodent Dilated Ischemic Cardiomyopathy Circulation, August 31, 2004; 110(9): 1083 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Barki-Harrington, C. Perrino, and H. A Rockman Network integration of the adrenergic system in cardiac hypertrophy Cardiovasc Res, August 15, 2004; 63(3): 391 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Pepe, O. W.V van den Brink, E. G Lakatta, and R.-P. Xiao Cross-talk of opioid peptide receptor and {beta}-adrenergic receptor signalling in the heart Cardiovasc Res, August 15, 2004; 63(3): 414 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Breit, M. Lagace, and M. Bouvier Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A Movsesian Altered cAMP-mediated signalling and its role in the pathogenesis of dilated cardiomyopathy Cardiovasc Res, June 1, 2004; 62(3): 450 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. El-Armouche, O. Zolk, T. Rau, and T. Eschenhagen Inhibitory G-proteins and their role in desensitization of the adenylyl cyclase pathway in heart failure Cardiovasc Res, December 1, 2003; 60(3): 478 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Foerster, F. Groner, J. Matthes, W. J. Koch, L. Birnbaumer, and S. Herzig Cardioprotection specific for the G protein Gi2 in chronic adrenergic signaling through {beta}2-adrenoceptors PNAS, November 25, 2003; 100(24): 14475 - 14480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-P. Xiao, S.-J. Zhang, K. Chakir, P. Avdonin, W. Zhu, R. A. Bond, C. W. Balke, E. G. Lakatta, and H. Cheng Enhanced Gi Signaling Selectively Negates {beta}2-Adrenergic Receptor (AR)- but Not {beta}1-AR-Mediated Positive Inotropic Effect in Myocytes From Failing Rat Hearts Circulation, September 30, 2003; 108(13): 1633 - 1639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Barbas, L. DesGroseillers, V. F. Castellucci, T. J. Carew, and S. Marinesco Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes Learn. Mem., September 1, 2003; 10(5): 373 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bartel, E.-G. Krause, G. Wallukat, and P. Karczewski New insights into {beta}2-adrenoceptor signaling in the adult rat heart Cardiovasc Res, March 1, 2003; 57(3): 694 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Cesetti, J. M. Hernandez-Guijo, P. Baldelli, V. Carabelli, and E. Carbone Opposite Action of beta 1- and beta 2-Adrenergic Receptors on CaV1 L-Channel Current in Rat Adrenal Chromaffin Cells J. Neurosci., January 1, 2003; 23(1): 73 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Gosmanov, J. A. Wong, and D. B. Thomason Duality of G protein-coupled mechanisms for beta -adrenergic activation of NKCC activity in skeletal muscle Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1025 - C1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Kilts, T. Akazawa, M. D. Richardson, and M. M. Kwatra Age Increases Cardiac Galpha i2 Expression, Resulting in Enhanced Coupling to G Protein-coupled Receptors J. Biol. Chem., August 16, 2002; 277(34): 31257 - 31262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. Jo, V. Leblais, P. H. Wang, M. T. Crow, and R.-P. Xiao Phosphatidylinositol 3-Kinase Functionally Compartmentalizes the Concurrent Gs Signaling During {beta}2-Adrenergic Stimulation Circ. Res., July 12, 2002; 91(1): 46 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zaugg, M. C. Schaub, T. Pasch, and D. R. Spahn Modulation of {beta}-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action Br. J. Anaesth., January 1, 2002; 88(1): 101 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Ostrom, C. Gregorian, R. M. Drenan, Y. Xiang, J. W. Regan, and P. A. Insel Receptor Number and Caveolar Co-localization Determine Receptor Coupling Efficiency to Adenylyl Cyclase J. Biol. Chem., November 2, 2001; 276(45): 42063 - 42069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-P. Xiao {beta}-Adrenergic Signaling in the Heart: Dual Coupling of the {beta}2-Adrenergic Receptor to Gs and Gi Proteins Sci. Signal., October 16, 2001; 2001(104): re15 - re15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Devic, Y. Xiang, D. Gould, and B. Kobilka beta -Adrenergic Receptor Subtype-Specific Signaling in Cardiac Myocytes from beta 1 and beta 2 Adrenoceptor Knockout Mice Mol. Pharmacol., September 1, 2001; 60(3): 577 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-S. Zhang, H.-J. Cheng, T. Ukai, H. Tachibana, and C.-P. Cheng Enhanced Cardiac L-Type Calcium Current Response to beta 2-Adrenergic Stimulation in Heart Failure J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 188 - 196. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Guimaraes and D. Moura Vascular Adrenoceptors: An Update Pharmacol. Rev., June 1, 2001; 53(2): 319 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-Z. Zhu, M. Zheng, W. J. Koch, R. J. Lefkowitz, B. K. Kobilka, and R.-P. Xiao Dual modulation of cell survival and cell death by beta 2-adrenergic signaling in adult mouse cardiac myocytes PNAS, February 13, 2001; 98(4): 1607 - 1612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chesley, M. S. Lundberg, T. Asai, R.-P. Xiao, S. Ohtani, E. G. Lakatta, and M. T. Crow The {beta}2-Adrenergic Receptor Delivers an Antiapoptotic Signal to Cardiac Myocytes Through Gi-Dependent Coupling to Phosphatidylinositol 3'-Kinase Circ. Res., December 8, 2000; 87(12): 1172 - 1179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-Y. Zhou, D. Yang, W.-Z. Zhu, S.-J. Zhang, D.-J. Wang, D. K. Rohrer, E. Devic, B. K. Kobilka, E. G. Lakatta, H. Cheng, et al. Spontaneous Activation of beta 2- but Not beta 1-Adrenoceptors Expressed in Cardiac Myocytes from beta 1beta 2 Double Knockout Mice Mol. Pharmacol., November 1, 2000; 58(5): 887 - 894. [Abstract] [Full Text]
|
|
|
|
|
|
K. Wenzel-Seifert and R. Seifert Molecular Analysis of beta 2-Adrenoceptor Coupling to Gs-, Gi-, and Gq-Proteins Mol. Pharmacol., November 1, 2000; 58(5): 954 - 966. [Abstract] [Full Text]
|
|
|
|
|
|
K. Nagata, C. Communal, C. C. Lim, M. Jain, T. M. Suter, F. R. Eberli, N. Satoh, W. S. Colucci, C. S. Apstein, and R. Liao Altered beta -adrenergic signal transduction in nonfailing hypertrophied myocytes from Dahl salt-sensitive rats Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2502 - H2508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Sosunov, R. Z. Gainullin, N.S. Moise, S. F. Steinberg, P. Danilo Jr., and M. R. Rosen {beta}1 and {beta}2-adrenergic receptor subtype effects in German shepherd dogs with inherited lethal ventricular arrhythmias Cardiovasc Res, November 1, 2000; 48(2): 211 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-P. Xiao Cell Logic for Dual Coupling of a Single Class of Receptors to Gs and Gi Proteins Circ. Res., October 13, 2000; 87(8): 635 - 637. [Full Text] [PDF]
|
|
|
|
|
|
J. D. Kilts, M. A. Gerhardt, M. D. Richardson, G. Sreeram, G. B. Mackensen, H. P. Grocott, W. D. White, R. D. Davis, M. F. Newman, J. G. Reves, et al. {beta}2-Adrenergic and Several Other G Protein-Coupled Receptors in Human Atrial Membranes Activate Both Gs and Gi Circ. Res., October 13, 2000; 87(8): 705 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Nagykaldi, D. Kem, R. Lazzara, and B. Szabo Conditioning of beta 1-adrenoceptor effect via beta 2-subtype on L-type Ca2+ current in canine ventricular myocytes Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1329 - H1337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hoque, M. A. Cook, and M. Karmazyn Inhibition of alpha 1-Adrenergic-Mediated Responses in Rat Ventricular Myocytes by Adenosine A1 Receptor Activation: Role of the KATP Channel J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 770 - 777. [Abstract] [Full Text]
|
|
|
|
|
|
M. Zaugg, W. Xu, E. Lucchinetti, S. A. Shafiq, N. Z. Jamali, and M. A. Q. Siddiqui {beta}-Adrenergic Receptor Subtypes Differentially Affect Apoptosis in Adult Rat Ventricular Myocytes Circulation, July 18, 2000; 102(3): 344 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. He, G. Wu, and M. C. Lapointe Isoproterenol and cAMP regulation of the human brain natriuretic peptide gene involves Src and Rac Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E1115 - E1123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Kim, M. D. Coyne, and J. K. Gwathmey Voltage-dependent calcium channels in ventricular cells of rainbow trout: effect of temperature changes in vitro Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2000; 278(6): R1524 - R1534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Ranu, J. C. W. Mak, P. J. Barnes, and S. E. Harding Gi-dependent suppression of beta 1-adrenoceptor effects in ventricular myocytes from NE-treated guinea pigs Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H1807 - H1814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Singh, C. Communal, D. B. Sawyer, and W. S. Colucci Adrenergic regulation of myocardial apoptosis Cardiovasc Res, February 1, 2000; 45(3): 713 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Meszaros, A. M. Gonzalez, Y. Endo-Mochizuki, S. Villegas, F. Villarreal, and L. L. Brunton Identification of G protein-coupled signaling pathways in cardiac fibroblasts: cross talk between Gq and Gs Am J Physiol Cell Physiol, January 1, 2000; 278(1): C154 - C162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O.-E. Brodde and M. C. Michel Adrenergic and Muscarinic Receptors in the Human Heart Pharmacol. Rev., December 1, 1999; 51(4): 651 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Communal, K. Singh, D. B. Sawyer, and W. S. Colucci Opposing Effects of {beta}1- and {beta}2-Adrenergic Receptors on Cardiac Myocyte Apoptosis : Role of a Pertussis Toxin-Sensitive G Protein Circulation, November 30, 1999; 100(22): 2210 - 2212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Cross, C. Steenbergen, R. J. Lefkowitz, W. J. Koch, and E. Murphy Overexpression of the Cardiac {beta}2-Adrenergic Receptor and Expression of a {beta}-Adrenergic Receptor Kinase-1 ({beta}ARK1) Inhibitor Both Increase Myocardial Contractility but Have Differential Effects on Susceptibility to Ischemic Injury Circ. Res., November 26, 1999; 85(11): 1077 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-P. Xiao, H. Cheng, Y.-Y. Zhou, M. Kuschel, and E. G. Lakatta Recent Advances in Cardiac {beta}2-Adrenergic Signal Transduction Circ. Res., November 26, 1999; 85(11): 1092 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Steinberg The Molecular Basis for Distinct {beta}-Adrenergic Receptor Subtype Actions in Cardiomyocytes Circ. Res., November 26, 1999; 85(11): 1101 - 1111. [Full Text] [PDF]
|
|
