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Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor.

Publication ,  Journal Article
Koch, WJ; Rockman, HA; Samama, P; Hamilton, RA; Bond, RA; Milano, CA; Lefkowitz, RJ
Published in: Science
June 2, 1995

Transgenic mice were created with cardiac-specific overexpression of the beta-adrenergic receptor kinase-1 (beta ARK1) or a beta ARK inhibitor. Animals overexpressing beta ARK1 demonstrated attenuation of isoproterenol-stimulated left ventricular contractility in vivo, dampening of myocardial adenylyl cyclase activity, and reduced functional coupling of beta-adrenergic receptors. Conversely, mice expressing the beta ARK inhibitor displayed enhanced cardiac contractility in vivo with or without isoproterenol. These animals demonstrate the important role of beta ARK in modulating in vivo myocardial function. Because increased amounts of beta ARK1 and diminished cardiac beta-adrenergic responsiveness characterize heart failure, these animals may provide experimental models to study the role of beta ARK in heart disease.

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Published In

Science

DOI

ISSN

0036-8075

Publication Date

June 2, 1995

Volume

268

Issue

5215

Start / End Page

1350 / 1353

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Ventricular Pressure
  • Sarcolemma
  • Receptors, Adrenergic, beta
  • Phenotype
  • Myocardium
  • Myocardial Contraction
  • Mice, Transgenic
  • Mice
  • Isoproterenol
 

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Koch, W. J., Rockman, H. A., Samama, P., Hamilton, R. A., Bond, R. A., Milano, C. A., & Lefkowitz, R. J. (1995). Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science, 268(5215), 1350–1353. https://doi.org/10.1126/science.7761854
Koch, W. J., H. A. Rockman, P. Samama, R. A. Hamilton, R. A. Bond, C. A. Milano, and R. J. Lefkowitz. “Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor.Science 268, no. 5215 (June 2, 1995): 1350–53. https://doi.org/10.1126/science.7761854.
Koch WJ, Rockman HA, Samama P, Hamilton RA, Bond RA, Milano CA, et al. Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science. 1995 Jun 2;268(5215):1350–3.
Koch, W. J., et al. “Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor.Science, vol. 268, no. 5215, June 1995, pp. 1350–53. Pubmed, doi:10.1126/science.7761854.
Koch WJ, Rockman HA, Samama P, Hamilton RA, Bond RA, Milano CA, Lefkowitz RJ. Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science. 1995 Jun 2;268(5215):1350–1353.
Journal cover image

Published In

Science

DOI

ISSN

0036-8075

Publication Date

June 2, 1995

Volume

268

Issue

5215

Start / End Page

1350 / 1353

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Ventricular Pressure
  • Sarcolemma
  • Receptors, Adrenergic, beta
  • Phenotype
  • Myocardium
  • Myocardial Contraction
  • Mice, Transgenic
  • Mice
  • Isoproterenol