Subtype-specific β-adrenoceptor signaling pathways in the heart and their potential clinical implications

Rui Ping Xiao, Weizhong Zhu, Ming Zheng, Khalid Chakir, Richard Bond, Edward Lakatta, Heping Cheng

Research output: Contribution to journalReview article

Abstract

β-Adrenoceptor stimulation serves as the most powerful means to increase cardiac output in response to stress or exercise. However, sustained β-adrenoceptor stimulation promotes pathological cardiac remodeling such as myocyte hypertrophy and apoptosis, thus contributing to heart failure. Coexisting cardiac β-adrenoceptor subtypes, mainly β1- adrenoceptors and β2-adrenoceptors, activate different signaling cascades with β1-adrenoceptors coupling to Gs and β2-adrenoceptors coupling to Gs and Gi pathways. As a result, sustained β2-adrenoceptor stimulation protects cardiomyocytes against apoptosis via a Gi- phosphatidylinositol 3-kinase-protein kinase B pathway, whereas chronic β1-adrenoceptor stimulation induces myocyte hypertrophy and apoptosis by protein kinase A-independent activation of calmodulin kinase II signaling. These advances in our understanding of β-adrenoceptor subtype signaling identify the mechanisms that underlie the beneficial effects of β-adrenoceptor antagonists and delineate the rationale for combining β1-adrenoceptor blockade with β2-adrenoceptor activation as a potential therapy for heart failure.

Original languageEnglish (US)
Pages (from-to)358-365
Number of pages8
JournalTrends in Pharmacological Sciences
Volume25
Issue number7
DOIs
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Adrenergic Receptors
Apoptosis
Muscle Cells
Hypertrophy
Heart Failure
Chemical activation
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
Calcium-Calmodulin-Dependent Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Cardiac Myocytes
Cardiac Output

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Subtype-specific β-adrenoceptor signaling pathways in the heart and their potential clinical implications. / Xiao, Rui Ping; Zhu, Weizhong; Zheng, Ming; Chakir, Khalid; Bond, Richard; Lakatta, Edward; Cheng, Heping.

In: Trends in Pharmacological Sciences, Vol. 25, No. 7, 07.2004, p. 358-365.

Research output: Contribution to journalReview article

Xiao, Rui Ping ; Zhu, Weizhong ; Zheng, Ming ; Chakir, Khalid ; Bond, Richard ; Lakatta, Edward ; Cheng, Heping. / Subtype-specific β-adrenoceptor signaling pathways in the heart and their potential clinical implications. In: Trends in Pharmacological Sciences. 2004 ; Vol. 25, No. 7. pp. 358-365.
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AU - Lakatta, Edward

AU - Cheng, Heping

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