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β-Adrenoceptor mediated signal transduction in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters

  • Chapter
Biochemistry of Signal Transduction in Myocardium

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 17))

Abstract

In view of the lack of information regarding the status of β-adrenoceptor mediated signal transduction mechanisms at severe stages of congestive heart failure, the status of β-adrenoceptors, G-proteins and adenylyl cyclase activities was examined in 220–275 day old cardiomyopathic hamster hearts. Although no changes in the Kd values for β1- and β2-adrenoceptors were seen, the number of β1-adrenoceptors, unlike that of β2-adrenoceptors, was markedly decreased in cardiac membranes from failing hearts. The activation of adenylyl cyclase in the failing hearts by different concentrations of isoproterenol was also attenuated in comparison to the control preparations. The basal adenylyl cyclase activity in cardiac membranes from the failing hearts was not altered; however, the stimulated enzyme activities, when measured in the presence of forskolin, NaF or Gpp(NH)p were depressed significantly. The functional activity of Gs-proteins (measured by cholera toxin stimulation of adenylyl cyclase) was depressed whereas that of Gi-proteins (measured by pertussis toxin stimulation of adenylyl cyclase) was increased in the failing hearts. Not only were the Gs- and Gi-protein contents (measured by immunoblotting) increased, the bioactivities of these proteins as determined by ADP-ribosylations in the presence of cholera toxin and pertussis toxin, respectively, were also higher in failing hearts in comparison to the control values. Northern blot analysis revealed that the signals for Gs- and Gi-protein mRNAs were augmented at this stage of heart failure. These results indicate that the loss of adrenergic support at severe stages of congestive heart failure in cardiomyopathic hamsters may involve a reduction in the number of β1-adrenoceptors, and an increase in Gi-protein contents as well as bioactivities in addition to an uncoupling of Gs-proteins from the catalytic site of adenylyl cyclase in cardiac membrane.

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Author information

Authors and Affiliations

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

    Deepak Kaura, Rajat Sethi, Xi Wang & Naranjan S. Dhalla

  2. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Deepak Kaura, Rajat Sethi, Xi Wang & Naranjan S. Dhalla

  3. Department of Internal Medicine, Aoto Hospital, Jikei University, Tokyo, Japan

    Nobuakira Takeda & Makoto Nagano

Authors
  1. Deepak Kaura
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  2. Nobuakira Takeda
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  3. Rajat Sethi
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  4. Xi Wang
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  5. Makoto Nagano
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  6. Naranjan S. Dhalla
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Editors and Affiliations

  1. Department of Biochemistry, Cardiovascular Research Institute COEUR, Faculty of Medicine of Health Science, Erasmus University Rotterdam, P.O. Box 1738, 3300 DR, Rotterdam, The Netherlands

    Jos M. J. Lamers

  2. Department of Cardiology, Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, P.O. Box 1738, 3300 DR, Rotterdam, The Netherlands

    Pieter D. Verdouw

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© 1996 Kluwer Academic Publishers

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Kaura, D., Takeda, N., Sethi, R., Wang, X., Nagano, M., Dhalla, N.S. (1996). β-Adrenoceptor mediated signal transduction in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters. In: Lamers, J.M.J., Verdouw, P.D. (eds) Biochemistry of Signal Transduction in Myocardium. Developments in Molecular and Cellular Biochemistry, vol 17. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1275-8_24

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  • DOI: https://doi.org/10.1007/978-1-4613-1275-8_24

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8544-1

  • Online ISBN: 978-1-4613-1275-8

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