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Journal of Molecular Medicine

, Volume 74, Issue 9, pp 489–495 | Cite as

Myocardial β-adrenergic receptor signaling in vivo: insights from transgenic mice

  • H. A. Rockman
  • W. J. Koch
  • C. A. Milano
  • R. J. Lefkowitz
Reviews

Abstract

Heart failure is a problem of increasing importance in cardiovascular medicine. An important characteristic of heart failure is reduced agonist-stimulated adenylyl cyclase activity (receptor desensitization) due to both diminished receptor number (receptor downregulation) and impaired receptor function (receptor uncoupling). These changes in the §-adrenergic receptor (§ AR) system may in part account for some of the abnormalities of contractile function in this disease. Myocardial contraction is closely regulated by G protein coupled β-adrenergic receptors through the action of the second messenger cAMP. The β-adrenergic receptors themselves are regulated by a set of specific kinases, termed the G protein-coupled receptor kinases. The study of this complex system in vivo has recently been advanced by the development of transgenic and gene targeted (“knock out”) mouse models. Combining transgenic technology with sophisticated physiological measurements of cardiac hemodynamics is an extremely powerful strategy to study the regulation of myocardial contractility in the normal and failing heart.

Key words

β-Adrenergic receptor β-Adrenergic receptor kinase G protein-coupled receptor kinase Transgenic mice Myocardial contractility 

Abbreviations

β-AR

β-Adrenergic receptor

GRK

G protein coupled receptor kinase

LV

Left ventricular

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • H. A. Rockman
    • 1
  • W. J. Koch
    • 2
  • C. A. Milano
    • 2
  • R. J. Lefkowitz
    • 3
  1. 1.Department of MedicineUniversity of California at San Diego, School of MedicineLa JollaUSA
  2. 2.Department of SurgeryDuke UniversityDurhamUSA
  3. 3.Howard Hughes Medical InstituteDuke UniversityDurhamUSA

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