Skip to main content

Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase.

Publication ,  Journal Article
Choi, DJ; Koch, WJ; Hunter, JJ; Rockman, HA
Published in: J Biol Chem
July 4, 1997

Pressure overload cardiac hypertrophy in the mouse was achieved following 7 days of transverse aortic constriction. This was associated with marked beta-adrenergic receptor (beta-AR) desensitization in vivo, as determined by a blunted inotropic response to dobutamine. Extracts from hypertrophied hearts had approximately 3-fold increase in cytosolic and membrane G protein-coupled receptor kinase (GRK) activity. Incubation with specific monoclonal antibodies to inhibit different GRK subtypes showed that the increase in activity could be attributed predominately to the beta-adrenergic receptor kinase (betaARK). Although overexpression of a betaARK inhibitor in hearts of transgenic mice did not alter the development of cardiac hypertrophy, the beta-AR desensitization associated with pressure overload hypertrophy was prevented. To determine whether the induction of betaARK occurred because of a generalized response to cellular hypertrophy, betaARK activity was measured in transgenic mice homozygous for oncogenic ras overexpression in the heart. Despite marked cardiac hypertrophy, no difference in betaARK activity was found in these mice overexpressing oncogenic ras compared with controls. Taken together, these data suggest that betaARK is a central molecule involved in alterations of beta-AR signaling in pressure overload hypertrophy. The mechanism for the increase in betaARK activity appears not to be related to the induction of cellular hypertrophy but to possibly be related to neurohumoral activation.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 4, 1997

Volume

272

Issue

27

Start / End Page

17223 / 17229

Location

United States

Related Subject Headings

  • ras Proteins
  • beta-Adrenergic Receptor Kinases
  • Receptors, Adrenergic, beta
  • Receptor Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Myocardial Contraction
  • Mice, Transgenic
  • Mice
  • Male
  • G-Protein-Coupled Receptor Kinase 5
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Choi, D. J., Koch, W. J., Hunter, J. J., & Rockman, H. A. (1997). Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase. J Biol Chem, 272(27), 17223–17229. https://doi.org/10.1074/jbc.272.27.17223
Choi, D. J., W. J. Koch, J. J. Hunter, and H. A. Rockman. “Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase.J Biol Chem 272, no. 27 (July 4, 1997): 17223–29. https://doi.org/10.1074/jbc.272.27.17223.
Choi DJ, Koch WJ, Hunter JJ, Rockman HA. Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase. J Biol Chem. 1997 Jul 4;272(27):17223–9.
Choi, D. J., et al. “Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase.J Biol Chem, vol. 272, no. 27, July 1997, pp. 17223–29. Pubmed, doi:10.1074/jbc.272.27.17223.
Choi DJ, Koch WJ, Hunter JJ, Rockman HA. Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase. J Biol Chem. 1997 Jul 4;272(27):17223–17229.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 4, 1997

Volume

272

Issue

27

Start / End Page

17223 / 17229

Location

United States

Related Subject Headings

  • ras Proteins
  • beta-Adrenergic Receptor Kinases
  • Receptors, Adrenergic, beta
  • Receptor Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Myocardial Contraction
  • Mice, Transgenic
  • Mice
  • Male
  • G-Protein-Coupled Receptor Kinase 5