(Circulation. 1999;100:2210.)
© 1999 American Heart Association, Inc.
Brief Rapid Communications |
Opposing Effects of ß1- and ß2-Adrenergic Receptors on Cardiac Myocyte Apoptosis
Role of a Pertussis Toxin–Sensitive G Protein
From the Myocardial Biology Unit and Cardiovascular Division, Boston University Medical Center, Boston Veterans Affairs Medical Center and Boston University School of Medicine, Boston, Mass.
Correspondence to Wilson S. Colucci, MD, Boston University Medical Center, 88 E Newton St, Boston, MA 02118. E-mail wilson.colucci{at}bmc.org
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Abstract |
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Background—ß-Adrenergic receptor (ß-AR) stimulation increases apoptosis in adult rat cardiac (ventricular) myocytes (ARVMs) via activation of adenylyl cyclase. ß2-ARs may couple to a Gi-mediated signaling pathway that can oppose the actions of adenylyl cyclase.
Methods and Results—In ARVMs, ß-AR stimulation for 24 hours increased the number of apoptotic cells as measured by flow cytometry. ß-AR–stimulated apoptosis was abolished by the ß1-AR–selective antagonist CGP 20712A (P<0.05 versus ß-AR stimulation alone) but was potentiated by the ß2-AR–selective antagonist ICI 118,551 (P<0.05 versus ß-AR stimulation alone). The muscarinic agonist carbachol also prevented ß-AR–stimulated apoptosis (P<0.05 versus ß-AR stimulation alone), whereas pertussis toxin potentiated the apoptotic action of ß-AR stimulation (P<0.05 versus ß-AR stimulation alone) and prevented the antiapoptotic action of carbachol.
Conclusions—In ARVMs, stimulation of ß1-ARs increases apoptosis via a cAMP-dependent mechanism, whereas stimulation of ß2-ARs inhibits apoptosis via a Gi-coupled pathway. These findings have implications for the pathophysiology and treatment of myocardial failure.
Key Words: apoptosis • receptors, adrenergic, beta • myocytes • adenylyl cyclase • proteins
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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We previously demonstrated that exposing adult rat ventricular myocytes (ARVMs) to norepinephrine (NE) for 24 hours increases the number of apoptotic cells.1 This effect is inhibited by the nonselective ß-adrenergic receptor (ß-AR) antagonist propranolol, mimicked by the adenylyl cyclase stimulator forskolin, and attenuated by an inhibitor of protein kinase A, indicating that NE stimulates apoptosis via a ß-AR–mediated increase in cAMP.1 Likewise, Iwai-Kanai et al2 showed that ß-AR stimulation increases apoptosis in neonatal rat cardiac myocytes by a mechanism that is dependent on the cAMP–protein kinase A pathway.
Both ß1- and ß2-ARs are expressed in cardiac myocytes and mediate an increase in contractility via Gs-dependent coupling to adenylyl cyclase.3 However, ß2-ARs can also couple to signaling pathways independent of cAMP or Gs and, in particular, to a pertussis toxin (PTX)–sensitive pathway mediated by Gi.4 5 6 We tested the hypotheses that (1) ß1- and ß2-AR subtypes exert opposing effects on apoptosis in cardiac myocytes and (2) ß2-AR activation attenuates ß1-AR–stimulated apoptosis via Gi. Accordingly, ARVMs were exposed to NE or isoproterenol in the presence of ß1- or ß2-AR–selective antagonists. Apoptosis was measured by flow cytometry and confirmed by terminal deoxynucleotidyl transferase (TdT)–mediated nick end-labeling (TUNEL).1 Carbachol and PTX were used to stimulate or inhibit Gi, respectively.
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Methods |
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Myocytes
ARVMs were isolated from the hearts of adult (200 to 220 g) male Sprague-Dawley rats,1 plated at a nonconfluent density of 30 to 50 cells/mm2 on 100-mm plastic culture dishes (Fisher) or 40x22-mm glass coverslips (Fisher) precoated with laminin (1 µg/cm2, Becton-Dickinson), and maintained in ACCT medium (DMEM; BSA, 2 mg/mL; L-carnitine, 2 mmol/L; creatine, 5 mmol/L; taurine, 5 mmol/L; penicillin, 100 IU/mL; streptomycin, 100 µg/mL) for 16 hours before drug treatments.
Drug Treatments
Myocytes were treated with isoproterenol (10 µmol/L) or a
combination of NE (10 µmol/L) and prazosin (PZ; 0.1
µmol/L, 30 minutes before NE) for 24 hours. All dishes were
supplemented with ascorbic acid (0.1 mmol/L). The
ß1-AR–selective antagonist CGP
20712A (0.3 µmol/L, RBI) or the
ß2-AR–selective antagonist ICI
118,551 (0.1 µmol/L, RBI) was added 30 minutes before NE.
Carbachol (30 µmol/L, Sigma) or PTX (1 µg/mL, Sigma) was added
30 minutes or 3 hours, respectively, before NE.
Flow Cytometry
Myocyte apoptosis was assessed primarily by flow
cytometry as described and validated.1 Apoptotic
cells stained with propidium iodide exhibit a reduced DNA content peak
in the hypodiploid region indicative of
apoptosis.7
TUNEL Staining
TUNEL staining was performed on cells plated on glass coverslips
with a Boehringer Mannheim in situ death detection
kit.1 The percentage of TUNEL-positive myocytes (relative
to total myocytes) was determined by counting 400 to 500 cells in 20
randomly chosen fields per coverslip on each of 3 coverslips for each
experiment.
Cellular cAMP Content
ARVMs (
2x105) were
homogenized at 4°C in buffer (Tris-HCl, 50 mmol/L;
MgCl2, 10 mmol/L; EDTA, 1 mmol/L; and
PMSF, 5 µmol/L; pH 7.4), and cAMP was measured by
radioimmunoassay (Dupont-NEN).
Statistics
All data are presented as mean±SEM. Differences among
multiple conditions were determined by 1-way ANOVA with a post hoc
Tukey’s test. Differences were considered significant if the null
hypothesis could be rejected at the 0.05 level.
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Results |
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ß-AR–Stimulated Apoptosis Is Mediated via ß1-ARs
Under control conditions,
6% to 7% of cells are
apoptotic, as indicated by a hypodiploid DNA
content.1 7
As we previously reported,1 treatment with NE/PZ for 24
hours increased the number of apoptotic myocytes by
1.72±0.08-fold (Figure 1A
). Pretreatment
with the ß1-AR–selective
antagonist CGP 20712A5 alone had no effect on
the number of apoptotic cells, but it inhibited the
apoptotic action of NE/PZ. Conversely, pretreatment with the
ß2-AR–selective antagonist ICI
118,5515 alone had no effect on the number of
apoptotic cells, but it potentiated the apoptotic
action of NE/PZ. Likewise, treatment with the nonselective ß-AR
agonist isoproterenol increased the number of apoptotic
myocytes by 1.81±0.08-fold (Figure 1B). As with NE/PZ, this
effect was inhibited by CGP 20712A and potentiated by ICI 118,551.
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Gi Attenuates ß-AR–Stimulated Apoptosis
Pretreatment with PTX had no effect on the number of
apoptotic myocytes, but it potentiated the apoptotic
action of NE/PZ as measured by flow cytometry (Figure 2A). Likewise, PTX pretreatment increased
the number of TUNEL-positive cells after NE/PZ (2.68±0.16-fold)
compared with NE alone (1.70±0.14-fold; P<0.05 versus
NE/PZ+PTX; n=3).
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Carbachol Protects From ß-AR–Stimulated Apoptosis
via Gi
Pretreatment with carbachol alone had no effect on the number of
apoptotic cells, but it abolished the apoptotic action
of NE/PZ (Figure 2B
). Pretreatment with PTX abolished the
protective effect of carbachol for NE-stimulated apoptosis.
Myocyte cAMP Content
cAMP content averaged 12.44±1.24 pmol/mg protein in control cells
and increased to 37.4±4.9 pmol/mg protein (P<0.05 versus
control) with NE/PZ. Pretreatment with PTX had no effect on basal cAMP
(11.1±1.2 pmol/mg protein) or that stimulated by NE/PZ (29.1±3.8
pmol/mg protein).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The major new findings of this study are that (1) ß1- and ß2-ARs mediate opposing effects of NE on apoptosis in cardiac myocytes (stimulation by ß1-ARs, inhibition by ß2-ARs) and (2) activation of a PTX-sensitive G protein (presumably Gi) by either ß2-ARs or carbachol inhibits ß-AR–stimulated apoptosis.
Opposing Effects of ß1-ARs and ß2-ARs
on Apoptosis
Both ß1- and
ß2-ARs can stimulate adenylyl cyclase by
coupling to Gs. Recently, it has been appreciated
that ß2- but not ß1-ARs
can also couple to non–adenylyl cyclase pathways via
Gi.4 The
Gi-mediated action may oppose the effect mediated
by Gs and in some cases may be the predominant
ß2-AR effect. Xiao and Lakatta3
showed that inhibition of Gi potentiated the
ability of ß2-AR stimulation to increase
contractility, intracellular calcium, and calcium
current in ARVMs. The coupling of ß2-ARs to
Gi may be regulated by a
Gs-mediated, protein kinase A–dependent
phosphorylation of the ß2-ARs
that favors coupling to Gi.4
Although NE and isoproterenol stimulate both
ß1- and ß2-ARs in
ARVMs, the net effect is to increase apoptosis. Because
ß1-ARs account for 80% of ß-ARs in
ARVMs,8 the predominance of the
ß1-AR effect on apoptosis may reflect
the stoichiometry of the subtypes.
ß1-AR–stimulated cAMP might also inhibit
non–cAMP-dependent pathways coupled to
ß2-ARs.6 9
Role of Gi
PTX, which inhibits Gi, increased the
magnitude of ß-AR–stimulated apoptosis and thus mimicked the
effect of ß2-AR blockade. Conversely,
pretreatment with carbachol, which stimulates Gi
in ARVMs via activation of M2 muscarinic
receptors, inhibited ß-AR–mediated apoptosis. The
antiapoptotic action of carbachol was abolished by PTX,
supporting the role of Gi.
Gi might oppose the actions of
Gs by inhibiting the activation of adenylyl
cyclase, which appears to be central to ß-AR–stimulated
apoptosis in cardiac myocytes.1 2 However, PTX did
not inhibit the ß-AR–stimulated increase in cAMP, suggesting that
Gi might inhibit ß-AR–stimulated
apoptosis via a cAMP-independent
mechanism.4 10
Implications
These findings support the thesis that increased sympathetic
activity to the myocardium contributes to myocardial
failure via ß1-AR–stimulated apoptosis
of cardiac myocytes. This premise is supported by the demonstration
that mice overexpressing Gs developed dilated
cardiomyopathy associated with myocyte
apoptosis,11 and mice overexpressing
ß1-ARs developed dilated
cardiomyopathy.12 13 In contrast, mice
overexpressing ß2-ARs did not develop
myocardial dysfunction at ages up to 4 months.14 Our
findings further demonstrate that activation of
Gi by a muscarinic agonist or
ß2-AR stimulation opposes the apoptotic
action of ß1-AR stimulation and thus raises the
possibility that strategies to activate
Gi or to increase the coupling of
Gi to ß2-ARs may be of
therapeutic value.
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Acknowledgments |
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This study was supported in part by NIH grants HL-52320, HL-42539, and HL-61639 (Dr Colucci), HL-057947 (Dr Singh), and HL-03878 (Dr Sawyer); a Grant-in-Aid from the AHA, Massachusetts Affiliate (Drs Singh and Sawyer); a Merit grant from the Department of Veterans Affairs (Dr Singh); and a fellowship from the AHA, Massachusetts Affiliate (Dr Communal).
Received August 26, 1999; revision received October 5, 1999; accepted October 8, 1999.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Communal C, Singh K, Pimentel DR, Colucci WS. Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the ß-adrenergic pathway. Circulation. 1998;98:1329–1334.
2.
Iwai-Kanai E, Hasegawa K, Araki M, Kakita T, Morimoto
T, Sasayama S. 
- and ß-Adrenergic pathways differentially
regulate cell type–specific apoptosis in rat cardiac myocytes.
Circulation. 1999;100:305–311.
3.
Xiao RP, Lakatta EG.
ß1-Adrenoreceptor stimulation
and ß2-adrenoreceptor
stimulation differ in their effects on contraction, cytosolic calcium,
and calcium current in single rat ventricular cells.
Circ Res. 1993;73:286–300.
4. Daaka Y, Luttrell LM, Lefkowitz RJ. Switching of the coupling of the ß2-adrenergic receptor to different G proteins by protein kinase A. Nature. 1997;390:88–91.[Medline] [Order article via Infotrieve]
5. Xiao RP, Ji X, Lakatta EG. Functional coupling of the ß2-adrenoreceptor to a pertussis toxin-sensitive G protein in cardiac myocytes. Mol Pharmacol. 1995;47:322–329.[Abstract]
6.
Xiao RP, Avdonin P, Zhou Y, Cheng H, Akhter SA,
Eschenhagen T, Lefkowitz RJ, Koch WJ, Lakatta EG. Coupling of
ß2-adrenoreceptor to
Gi protein and its
physiological relevance to murine cardiac myocytes.
Circ Res. 1999;84:43–52.
7. Fraker PJ, King LE, Lill-Elghanian D, Telford WG. Quantification of apoptotic events in pure and heterogeneous populations of cells using the flow cytometer. Methods Cell Biol. 1995;46:57–76.[Medline] [Order article via Infotrieve]
8.
Kuznetsov V, Pak E, Robinson RB, Steinberg SF.
ß2-Adrenergic receptor actions in neonatal and
adult rat ventricular myocytes. Circ Res. 1995;76:40–52.
9.
Wu J, Dent P, Jelinek T, Wolfman A, Weber MJ, Sturgill
TW. Inhibition of the EGF-activated MAP kinase signaling
pathway by adenosine 3',5'-monophosphate. Science. 1993;262:1065–1069.
10.
Luttrell LM, Ferguson SSG, Daaka Y, Miller WE, Maudsley
S, Della Rocca GJ, Lin F-T, Kawakatsu H, Owada K, Luttrell DK, Caron
MG, Lefkowitz RJ. ß-Arrestin-dependent formation of
ß2 adrenergic receptor-Src protein kinase
complexes. Science. 1999;283:655–661.
11.
Geng Y, Ishikawa Y, Vatner DE, Wagner TE, Bishop SP,
Vatner SF, Homcy CJ. Apoptosis of cardiac myocytes in
Gs alpha transgenic mice. Circ Res. 1999;84:34–42.
12. Port JD, Weinberger HD, Bisognano JD, Knudson OA, Bohlmeyer TJ, Pende A, Bristow MR. Echocardiographic and histopathological characterization of young and old transgenic mice over-expressing the human ß1-adrenergic receptor. J Am Coll Cardiol. 1998;31:177A. Abstract.
13.
Engelhardt S, Hein L, Wiesmann F, Lohse MJ. Progressive
hypertrophy and heart failure in
ß1-adenergic receptor transgenic mice.
Proc Natl Acad Sci U S A. 1999;96:7059–7064.
14. Rockman HA, Hamilton RA, Jones LR, Milano CA, Mao L, Lefkowitz RJ. Enhanced myocardial relaxation in vivo in transgenic mice overexpressing the beta2-adrenergic receptor is associated with reduced phospholamban protein. J Clin Invest. 1996;97:1618–1623.[Medline] [Order article via Infotrieve]
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|
 C. M. Filipeanu, F. Zhou, M. L. Lam, K. E. Kerut, W. C. Claycomb, and G. Wu Enhancement of the Recycling and Activation of beta-Adrenergic Receptor by Rab4 GTPase in Cardiac Myocytes J. Biol. Chem., April 21, 2006; 281(16): 11097 - 11103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. He, M. Bellini, H. Inuzuka, J. Xu, Y. Xiong, X. Yang, A. M. Castleberry, and R. A. Hall Proteomic Analysis of beta1-Adrenergic Receptor Interactions with PDZ Scaffold Proteins J. Biol. Chem., February 3, 2006; 281(5): 2820 - 2827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Menon, M. Singh, R. S. Ross, J. N. Johnson, and K. Singh {beta}-Adrenergic receptor-stimulated apoptosis in adult cardiac myocytes involves MMP-2-mediated disruption of {beta}1 integrin signaling and mitochondrial pathway Am J Physiol Cell Physiol, January 1, 2006; 290(1): C254 - C261. [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]
|
|
|
|
|
|
Y.-T. Tseng, N. Yano, A. Rojan, J. P. Stabila, B. G. McGonnigal, V. Ianus, R. Wadhawan, and J. F. Padbury Ontogeny of phosphoinositide 3-kinase signaling in developing heart: effect of acute {beta}-adrenergic stimulation Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1834 - H1842. [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]
|
|
|
|
|
|
J.-Q. He, R. C. Balijepalli, R. A. Haworth, and T. J. Kamp Crosstalk of {beta}-Adrenergic Receptor Subtypes Through Gi Blunts {beta}-Adrenergic Stimulation of L-Type Ca2+ Channels in Canine Heart Failure Circ. Res., September 16, 2005; 97(6): 566 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. McConville, R. G. Spencer, and E. G. Lakatta Temporal dynamics of inotropic, chronotropic, and metabolic responses during {beta}1- and {beta}2-AR stimulation in the isolated, perfused rat heart Am J Physiol Endocrinol Metab, September 1, 2005; 289(3): E412 - E418. [Abstract] [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. Ding, J.-i. Abe, H. Wei, Q. Huang, R. A. Walsh, C. A. Molina, A. Zhao, J. Sadoshima, B. C. Blaxall, B. C. Berk, et al. Functional Role of Phosphodiesterase 3 in Cardiomyocyte Apoptosis: Implication in Heart Failure Circulation, May 17, 2005; 111(19): 2469 - 2476. [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]
|
|
|
|
 |
|
 K. Machida, H. Inoue, K. Matsumoto, M. Tsuda, S. Fukuyama, H. Koto, H. Aizawa, Y. Kureishi, N. Hara, and Y. Nakanishi Activation of PI3K-Akt pathway mediates antiapoptotic effects of {beta}-adrenergic agonist in airway eosinophils Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L860 - L867. [Abstract] [Full Text] [PDF]
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|
|
|
|
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L. Wang, Y.-H. Feng, and G. I. Gorodeski Epidermal Growth Factor Facilitates Epinephrine Inhibition of P2X7-Receptor-Mediated Pore Formation and Apoptosis: A Novel Signaling Network Endocrinology, January 1, 2005; 146(1): 164 - 174. [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]
|
|
|
|
|
|
K. Iwatsubo, S. Minamisawa, T. Tsunematsu, M. Nakagome, Y. Toya, J. E. Tomlinson, S. Umemura, R. M. Scarborough, D. E. Levy, and Y. Ishikawa Direct Inhibition of Type 5 Adenylyl Cyclase Prevents Myocardial Apoptosis without Functional Deterioration J. Biol. Chem., September 24, 2004; 279(39): 40938 - 40945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Covolo, U. Gelatti, M. Metra, S. Nodari, A. Piccichè, N. Pezzali, C. Zani, A. Alberti, F. Donato, G. Nardi, et al. Role of {beta}1- and {beta}2-adrenoceptor polymorphisms in heart failure: a case-control study Eur. Heart J., September 1, 2004; 25(17): 1534 - 1541. [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]
|
|
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|
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|
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]
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M. Ito, T. Adachi, D. R. Pimentel, Y. Ido, and W. S. Colucci Statins Inhibit {beta}-Adrenergic Receptor-Stimulated Apoptosis in Adult Rat Ventricular Myocytes via a Rac1-Dependent Mechanism Circulation, July 27, 2004; 110(4): 412 - 418. [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]
|
|
|
|
 |
|
 J. F. Heubach, U. Ravens, and A. J. Kaumann Epinephrine Activates Both Gs and Gi Pathways, but Norepinephrine Activates Only the Gs Pathway through Human {beta}2-Adrenoceptors Overexpressed in Mouse Heart Mol. Pharmacol., May 1, 2004; 65(5): 1313 - 1322. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
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|
|
|
|
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]
|
|
|
|
|
|
M. J. Lohse, S. Engelhardt, and T. Eschenhagen What Is the Role of {beta}-Adrenergic Signaling in Heart Failure? Circ. Res., November 14, 2003; 93(10): 896 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pavoine, N. Behforouz, C. Gauthier, S. Le Gouvello, F. Roudot-Thoraval, C. R. Martin, A. Pawlak, C. Feral, N. Defer, R. Houel, et al. {beta}2-Adrenergic Signaling in Human Heart: Shift from the Cyclic AMP to the Arachidonic Acid Pathway Mol. Pharmacol., November 1, 2003; 64(5): 1117 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Liang, S. Austin, Q. Hoang, and P. H. Fishman Resistance of the Human {beta}1-Adrenergic Receptor to Agonist-mediated Down-regulation: ROLE OF THE C TERMINUS IN DETERMINING {beta}-SUBTYPE DEGRADATION J. Biol. Chem., October 10, 2003; 278(41): 39773 - 39781. [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]
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|
|
|
O. Manfrini, C. Pizzi, D. Trere, F. Fontana, and R. Bugiardini Parasympathetic failure and risk of subsequent coronary events in unstable angina and non-ST-segment elevation myocardial infarction Eur. Heart J., September 1, 2003; 24(17): 1560 - 1566. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
C. Maack, M. Bohm, L. Vlaskin, E. Dabew, K. Lorenz, H.-J. Schafers, M. J. Lohse, and S. Engelhardt Partial Agonist Activity of Bucindolol Is Dependent on the Activation State of the Human {beta}1-Adrenergic Receptor Circulation, July 22, 2003; 108(3): 348 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Hu, W. Chen, N. P. Martin, E. J. Whalen, R. T. Premont, and R. J. Lefkowitz GIPC Interacts with the {beta}1-Adrenergic Receptor and Regulates {beta}1-Adrenergic Receptor-mediated ERK Activation J. Biol. Chem., July 3, 2003; 278(28): 26295 - 26301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Abbate, G. G. L. Biondi-Zoccai, R. Bussani, A. Dobrina, D. Camilot, F. Feroce, R. Rossiello, F. Baldi, F. Silvestri, L. M. Biasucci, et al. Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure J. Am. Coll. Cardiol., March 5, 2003; 41(5): 753 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Remondino, S. H. Kwon, C. Communal, D. R. Pimentel, D. B. Sawyer, K. Singh, and W. S. Colucci {beta}-Adrenergic Receptor-Stimulated Apoptosis in Cardiac Myocytes Is Mediated by Reactive Oxygen Species/c-Jun NH2-Terminal Kinase-Dependent Activation of the Mitochondrial Pathway Circ. Res., February 7, 2003; 92(2): 136 - 138. [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]
|
|
|
|
 |
|
 M. L. Kukin {beta}-Blockers in Chronic Heart Failure: Considerations for Selecting an Agent Mayo Clin. Proc., November 1, 2002; 77(11): 1199 - 1206. [Abstract] [PDF]
|
|
|
|
|
|
P. Chiari, V. Piriou, G. Hadour, C. Rodriguez, J. Loufouat, J.-J. Lehot, M. Ovize, and R. Ferrera Preservation of ischemia and isoflurane-induced preconditioning after brain death in rabbit hearts Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1769 - H1774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xiang, V. O. Rybin, S. F. Steinberg, and B. Kobilka Caveolar Localization Dictates Physiologic Signaling of beta 2-Adrenoceptors in Neonatal Cardiac Myocytes J. Biol. Chem., September 6, 2002; 277(37): 34280 - 34286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Levin, S. Marullo, O. Muntaner, B. Andersson, and Y. Magnusson The Myocardium-protective Gly-49 Variant of the beta 1-Adrenergic Receptor Exhibits Constitutive Activity and Increased Desensitization and Down-regulation J. Biol. Chem., August 16, 2002; 277(34): 30429 - 30435. [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]
|
|
|
|
|
|
E. N Dedkova, Y. Gao Wang, L. A Blatter, and S. L Lipsius Nitric oxide signalling by selective {beta}2-adrenoceptor stimulation prevents ACh-induced inhibition of {beta}2-stimulated Ca2+ current in cat atrial myocytes J. Physiol., August 1, 2002; 542(3): 711 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yusta, J. Estall, and D. J. Drucker Glucagon-like Peptide-2 Receptor Activation Engages Bad and Glycogen Synthase Kinase-3 in a Protein Kinase A-dependent Manner and Prevents Apoptosis following Inhibition of Phosphatidylinositol 3-Kinase J. Biol. Chem., July 5, 2002; 277(28): 24896 - 24906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. A. Janssen and J. F. M. Smits Autonomic control of blood pressure in mice: basic physiology and effects of genetic modification Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1545 - R1564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gong, H. Sun, W. J. Koch, T. Rau, T. Eschenhagen, U. Ravens, J. F. Heubach, D. L. Adamson, and S. E. Harding Specific {beta}2AR Blocker ICI 118,551 Actively Decreases Contraction Through a Gi-Coupled Form of the {beta}2AR in Myocytes From Failing Human Heart Circulation, May 28, 2002; 105(21): 2497 - 2503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Andreka, N. Aiyar, L. C. Olson, J. Q. Wei, M. S. Turner, K. A. Webster, E. H. Ohlstein, and N. H. Bishopric Bucindolol Displays Intrinsic Sympathomimetic Activity in Human Myocardium Circulation, May 21, 2002; 105(20): 2429 - 2434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Goldstein Benefits of {beta}-Blocker Therapy for Heart Failure: Weighing the Evidence Arch Intern Med, March 25, 2002; 162(6): 641 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-M. Zhang, Z. Wang, and S. Nattel Effects of sustained beta -adrenergic stimulation on ionic currents of cultured adult guinea pig cardiomyocytes Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H880 - H889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A Nikolaidis, T. Hentosz, A. Doverspike, R. Huerbin, C. Stolarski, Y.-T. Shen, and R. P Shannon Catecholamine stimulation is associated with impaired myocardial O2 utilization in heart failure Cardiovasc Res, February 1, 2002; 53(2): 392 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Andersson, B Gruner Svealv, M Scharin Tang, and R Mobini Longitudinal myocardial contraction improves early during titration with metoprolol CR/XL in patients with heart failure Heart, January 1, 2002; 87(1): 23 - 28. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
P. K. Tithof, M. Elgayyar, H. M. Schuller, M. Barnhill, and R. Andrews 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone, a nicotine derivative, induces apoptosis of endothelial cells Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1946 - H1954. [Abstract] [Full Text] [PDF]
|
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|
|
 |
|
 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]
|
|
|
|
|
|
A. D. Eckhart and W. J. Koch Transgenic Studies of Cardiac Adrenergic Receptor Regulation J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 1 - 5. [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]
|
|
|
|
|
|
F. Qin, N. K. Rounds, W. Mao, K. Kawai, and C.-s. Liang Antioxidant vitamins prevent cardiomyocyte apoptosis produced by norepinephrine infusion in ferrets Cardiovasc Res, September 1, 2001; 51(4): 736 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Hare Oxidative Stress and Apoptosis in Heart Failure Progression Circ. Res., August 3, 2001; 89(3): 198 - 200. [Full Text] [PDF]
|
|
|
|
|
|
X.-J. Du Sympathoadrenergic mechanisms in functional regulation and development of cardiac hypertrophy and failure: findings from genetically engineered mice Cardiovasc Res, June 1, 2001; 50(3): 443 - 453. [Full Text] [PDF]
|
|
|
|
|
|
D. M. Kaye, L. Johnston, G. Vaddadi, H. Brunner-LaRocca, G. L. Jennings, and M. D. Esler Mechanisms of Carvedilol Action in Human Congestive Heart Failure Hypertension, May 1, 2001; 37(5): 1216 - 1221. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
M. Henaff, S. N. Hatem, and J.-J. Mercadier Low Catecholamine Concentrations Protect Adult Rat Ventricular Myocytes against Apoptosis through cAMP-Dependent Extracellular Signal-Regulated Kinase Activation Mol. Pharmacol., April 13, 2001; 58(6): 1546 - 1553. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Jain, C. C. Lim, K. Nagata, V. M. Davis, D. S. Milstone, R. Liao, and R. M. Mortensen Targeted inactivation of G{alpha}i does not alter cardiac function or {beta}-adrenergic sensitivity Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H569 - H575. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
M. Schafer, K. Ponicke, I. Heinroth-Hoffmann, O.-E. Brodde, H. M. Piper, and K.-D. Schluter Beta-adrenoceptor stimulation attenuates the hypertrophic effect of alpha-adrenoceptor stimulation in adult rat ventricular cardiomyocytes J. Am. Coll. Cardiol., January 1, 2001; 37(1): 300 - 307. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
Y.-Y. Zhou and M. Artman Nucleoside diphosphate kinase: a new player in heart failure? Cardiovasc Res, January 1, 2001; 49(1): 7 - 10. [Full Text] [PDF]
|
|
|
|
|
|
S. F. Steinberg The Cellular Actions of {beta}-Adrenergic Receptor Agonists : Looking Beyond cAMP Circ. Res., December 8, 2000; 87(12): 1079 - 1082. [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]
|
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|
X.-J. Du, X.-M. Gao, B. Wang, G. L Jennings, E. A Woodcock, and A. M Dart Age-dependent cardiomyopathy and heart failure phenotype in mice overexpressing {beta}2-adrenergic receptors in the heart Cardiovasc Res, December 1, 2000; 48(3): 448 - 454. [Abstract] [Full Text] [PDF]
|
|
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|
|
|
N.G. Mahon and W.J. Mckenna Genes and acquired disease: beta-adrenoceptor polymorphisms and heart failure Eur. Heart J., November 2, 2000; 21(22): 1810 - 1812. [PDF]
|
|
|
|
|
|
H. N. Sabbah, V. G. Sharov, R. C. Gupta, A. Todor, V. Singh, and S. Goldstein Chronic therapy with metoprolol attenuates cardiomyocyte apoptosis in dogs with heart failure J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1698 - 1705. [Abstract] [Full Text] [PDF]
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