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Citations to this article

Overexpression of myocardial Gsalpha prevents full expression of catecholamine desensitization despite increased beta-adrenergic receptor kinase.
D E Vatner, … , C J Homcy, S F Vatner
D E Vatner, … , C J Homcy, S F Vatner
Published May 1, 1998
Citation Information: J Clin Invest. 1998;101(9):1916-1922. https://doi.org/10.1172/JCI1530.
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Research Article

Overexpression of myocardial Gsalpha prevents full expression of catecholamine desensitization despite increased beta-adrenergic receptor kinase.

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Abstract

Inotropic and chronotropic responses to catecholamines in young adult transgenic mice overexpressing myocardial Gsalpha are enhanced. One might predict that over the life of the animal, this chronically enhanced beta-adrenergic receptor stimulation would result in homologous catecholamine desensitization. To test this hypothesis, old transgenic Gsalpha mice and age-matched controls were studied physiologically in terms of responsiveness of left ventricular function (ejection fraction) to isoproterenol in vivo and in vitro in terms of beta-adrenergic receptor signaling. Old transgenic mice still responded to isoproterenol with augmented (P < 0.05) left ventricular ejection fraction (+44+/-3%) compared with age-matched controls (+24+/-1%). Although total beta-adrenergic receptor density was reduced in the old transgenic mice, and G protein receptor kinase 2 (beta-adrenergic receptor kinase) levels were increased, the fraction of receptors binding agonist with high affinity as well as isoproterenol- and G protein-stimulated adenylyl cyclase activities were enhanced. Thus, classical catecholamine desensitization is not effective in attenuation of persistently enhanced responses to sympathetic stimulation in mice overexpressing myocardial Gsalpha. To support this conclusion further, experiments were performed with chronic isoproterenol, which elicited effective desensitization in wild-type controls, but failed to elicit desensitization in overexpressed Gsalpha mice. The results of this study suggest that the lack of protective desensitization mechanisms may be responsible in part for the dilated cardiomyopathy which develops with chronic sympathetic stress over the life of these animals.

Authors

D E Vatner, K Asai, M Iwase, Y Ishikawa, T E Wagner, R P Shannon, C J Homcy, S F Vatner

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Total citations by year

Year: 2022 2020 2014 2011 2009 2008 2005 2004 2003 2002 2001 2000 1999 Total
Citations: 1 1 1 1 2 1 6 3 3 2 3 5 7 36
Citation information
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Citations to this article (36)

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American journal of physiology. Cell physiology 2022
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UH Frey, JD Muehlschlegel, C Ochterbeck, AA Fox, SK Shernan, CD Collard, P Lichtner, J Peters, S Body
Anesthesiology 2014
Genetic interactions in the  -adrenoceptor/G-protein signal transduction pathway and survival after coronary artery bypass grafting: a pilot study
UH Frey, E Kottenberg, M Kamler, K Leineweber, I Manthey, G Heusch, W Siffert, J Peters
British Journal of Anaesthesia 2011
Progressive loss of creatine maintains a near normal DeltaG approximately (ATP) in transgenic mouse hearts with cardiomyopathy caused by overexpressing Gsalpha
W Shen, DE Vatner, SF Vatner, JS Ingwall
Journal of Molecular and Cellular Cardiology 2009
A novel functional haplotype in the human GNAS gene alters G s expression, responsiveness to  -adrenoceptor stimulation, and peri-operative cardiac performance
UH Frey, M Adamzik, E Kottenberg-Assenmacher, H Jakob, I Manthey, M Broecker-Preuss, L Bergmann, G Heusch, W Siffert, J Peters, K Leineweber
European Heart Journal 2009
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P Ostasov, J Krusek, D Durchankova, P Svoboda, J Novotny
Cell Biochemistry and Function 2008
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EL Germain-Lee, W Schwindinger, JL Crane, R Zewdu, LS Zweifel, G Wand, DL Huso, M Saji, MD Ringel, MA Levine
Endocrinology 2005
Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos
A Meyer, FJ Seidler, JE Aldridge, TA Slotkin
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Neuropsychopharmacology 2005
Imbalances emerge in cardiac autonomic cell signaling after neonatal exposure to terbutaline or chlorpyrifos, alone or in combination
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Developmental Brain Research 2005
Mammalian G Proteins and Their Cell Type Specific Functions
N Wettschureck, S Offermanns
Physiological reviews 2005
Strain-dependent β-adrenergic receptor function influences myocardial responses to isoproterenol stimulation in mice
MD Faulx, P Ernsberger, D Vatner, RD Hoffman, W Lewis, R Strachan, BD Hoit
American journal of physiology. Heart and circulatory physiology 2005
Mouse models to study G-protein-mediated signaling
N Wettschureck, A Moers, S Offermanns
Pharmacology & Therapeutics 2004
Critical periods for chlorpyrifos-induced developmental neurotoxicity: alterations in adenylyl cyclase signaling in adult rat brain regions after gestational or neonatal exposure
A Meyer, FJ Seidler, JE Aldridge, CA Tate, MM Cousins, TA Slotkin
Environmental Health Perspectives 2004
Transgenic Models in Pharmacology
S Offermanns, L Hein
2004
G-proteins as transducers in transmembrane signalling
S Offermanns
Progress in Biophysics and Molecular Biology 2003
Critical Periods for Chlorpyrifos-Induced Developmental Neurotoxicity: Alterations in Adenylyl Cyclase Signaling in Adult Rat Brain Regions after Gestational or Neonatal Exposure
A Meyer, FJ Seidler, JE Aldridge, CA Tate, MM Cousins, TA Slotkin
Environmental Health Perspectives 2003
Ontogenesis of β-Adrenoceptor Signaling: Implications for Perinatal Physiology and for Fetal Effects of Tocolytic Drugs
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The Journal of pharmacology and experimental therapeutics 2003
β-Adrenoceptor control of G protein function in the neonate: determinant of desensitization or sensitization
JT Auman, FJ Seidler, TA Slotkin
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 2002
Accelerated Cardiomyopathy in Mice With Overexpression of Cardiac G s α and a Missense Mutation in the α-Myosin Heavy Chain
SE Hardt, YJ Geng, O Montagne, K Asai, C Hong, GP Yang, SP Bishop, SJ Kim, DE Vatner, CE Seidman, JG Seidman, CJ Homcy, SF Vatner
Circulation 2002
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M Iwase, M Yokota, K Kitaichi, L Wang, K Takagi, T Nagasaka, H Izawa, T Hasegawa
Critical Care Medicine 2001
Role of lysophosphatidylcholine in the desensitization of beta-adrenergic receptors by Ca(2+) sensitization in tracheal smooth muscle
H Kume, S Ito, Y Ito, K Yamaki
American journal of respiratory cell and molecular biology 2001
Altered Beta-adrenergic Receptor Gene Regulation and Signaling in Chronic Heart Failure
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Journal of Molecular and Cellular Cardiology 2001
Viral-Mediated Gene Delivery Of Constitutively Activated GAlphaS Alters Vasoreactivity
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Clinical and Experimental Pharmacology and Physiology 2000
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Inhibition of Spontaneous β 2 -Adrenergic Activation Rescues β 1 -Adrenergic Contractile Response in Cardiomyocytes Overexpressing β 2 -Adrenoceptor
SJ Zhang, H Cheng, YY Zhou, DJ Wang, W Zhu, B Ziman, H Spurgoen, RJ Lefkowitz, EG Lakatta, WJ Koch, RP Xiao
The Journal of biological chemistry 2000
β-Adrenergic Receptor Signaling: An Acute Compensatory Adjustment—Inappropriate for the Chronic Stress of Heart Failure?: Insights from Gsα Overexpression and Other Genetically Engineered Animal Models
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Determinants of the Cardiomyopathic Phenotype in Chimeric Mice Overexpressing Cardiac Gsα
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Circulation research 2000
Differential regulation of inotropy and lusitropy in overexpressed Gsα myocytes through cAMP and Ca2+ channel pathways
SJ Kim, A Yatani, DE Vatner, S Yamamoto, Y Ishikawa, TE Wagner, RP Shannon, YK Kim, G Takagi, K Asai, CJ Homcy, SF Vatner
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Overexpression of the G protein G11α prevents desensitization of CA2+ response to thyrotropin-releasing hormone
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Beta-adrenergic receptor-G protein-adenylyl cyclase signal transduction in the failing heart
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Recent Advances in Cardiac β 2 -Adrenergic Signal Transduction
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Circulation research 1999
Apoptosis of Cardiac Myocytes in Gsα Transgenic Mice
YJ Geng, Y Ishikawa, DE Vatner, TE Wagner, SP Bishop, SF Vatner, CJ Homcy
Circulation research 1999

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