Regulation of contractility and metabolic signaling by the β2-adrenergic receptor in rat ventricular muscle

Joaquín Pérez-Schindler, Andrew Philp, Keith Baar, Jesús Hernández-Cascales

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Aims: Cardiac function is modulated by the sympathetic nervous system through β-adrenergic receptor (β-AR) activity and this represents the main regulatory mechanism for cardiac performance. To date, however, the metabolic and molecular responses to β2-agonists are not well characterized. Therefore, we studied the inotropic effect and signaling response to selective β2-AR activation by tulobuterol. Main methods: Strips of rat right ventricle were electrically stimulated (1 Hz) in standard Tyrode solution (95% O2, 5% CO2) in the presence of the β1-antagonist CGP-20712A (1 μM). A cumulative dose-response curve for tulobuterol (0.1-10 μM), in the presence or absence of the phosphodiesterase (PDE) inhibitor IBMX (30 μM), or 10 min incubation (1 μM) with the β2-agonist tulobuterol was performed. Key findings: β2-AR stimulation induced a positive inotropic effect (maximal effect = 33 ± 3.3%) and a decrease in the time required for half relaxation (from 45 ± 0.6 to 31 ± 1.8 ms, - 30%, p < 0.001) after the inhibition of PDEs. After 10 min of β2-AR stimulation, p-AMPKαT172 (54%), p-PKBT308 (38%), p-AS160 T642 (46%) and p-CREBS133 (63%) increased, without any change in p-PKAT197. Significance: These results suggest that the regulation of ventricular contractility is not the primary function of the β2-AR. Rather, β2-AR could function to activate PKB and AMPK signaling, thereby modulating muscle mass and energetic metabolism of rat ventricular muscle.

Original languageEnglish (US)
Pages (from-to)892-897
Number of pages6
JournalLife Sciences
Volume88
Issue number19-20
DOIs
StatePublished - May 9 2011

Keywords

  • β-adrenergic receptor
  • AMPK
  • Cardiac contractility
  • Cardiac metabolism
  • PI3K

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Regulation of contractility and metabolic signaling by the β<sub>2</sub>-adrenergic receptor in rat ventricular muscle'. Together they form a unique fingerprint.

  • Cite this