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Heart Failure pp 209-218 | Cite as

β-Adrenergic Receptor Desensitization in Cardiac Disease: Insights from Gene-Targeted Mice

  • Dong-Ju Choi
  • Walter J. Koch
  • Howard A. Rockman
Conference paper

Abstract

β-Adrenergic receptors (βARS) belong to the large family of G-protein-coupled receptors that form the interface between the sympathetic nervous system and the cardiovascular system. Binding of β-agonists to the βAR leads to activation of adenylyl cyclase, generating cAMP and activating cAMP-dependent protein kinase A (PKA). Phosphorylation of critical regulatory proteins by PKA acts in concert to increase the rate of contraction, peak force, and the rate of relaxation. The regulation of myocardial βARS involves a process characterized by a rapid loss of receptor responsiveness despite continued presence of agonist. Chronic human heart failure is characterized by marked βAR receptor desensitization as the result of both diminished βAR number (receptor downregulation) and impaired βAR function (receptor uncoupling). This review focuses on some recent studies using gene-targeted mouse models to understand the role of the βAR system in pathological conditions of cardiac hypertrophy and heart failure.

Key words

βAR receptor desensitization Cardiac hypertrophy Heart failure Gene-targeted mouse models 

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Copyright information

© Springer-Verlag Tokyo 2000

Authors and Affiliations

  • Dong-Ju Choi
    • 1
  • Walter J. Koch
    • 2
  • Howard A. Rockman
    • 3
  1. 1.Department of Medicine and Cardiovascular Research InstituteGyeong-Sang National UniversityChinjuKorea
  2. 2.Department of SurgeryDuke UniversityDurhamUSA
  3. 3.Department of MedicineDuke UniversityDurhamUSA

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