Agonist-specific activation of the beta2-adrenoceptor/Gs-protein and beta2-adrenoceptor/Gi-protein pathway in adult rat ventricular cardiomyocytes

Br J Pharmacol. 2006 Apr;147(7):714-9. doi: 10.1038/sj.bjp.0706674.


In rat ventricular cardiomyocytes beta2-adrenoceptors (AR) couple to Gs- and Gi-protein, and evidence has accumulated that beta2-AR agonists can differentially activate either Gs- or Gs- and Gi-protein. In this study, in isolated adult rat ventricular cardiomyocytes, we assessed the effects of pertussis toxin (PTX) on beta2-AR agonist (terbutaline (TER), salbutamol (SAL) and fenoterol (FEN)) evoked inhibition of phenylephrine (PE)-induced increase in the rate of protein synthesis (assessed as [3H]phenylalanine incorporation) to find out which beta2-AR agonist activates selectively Gs- or Gs- and Gi-protein. PE (1 microM) increased the rate of protein synthesis from 100% to 130+/-2% (n = 34). FEN, TER and SAL (1 nM-10 microM) inhibited PE-induced increase in the rate of protein synthesis concentration-dependently. FEN inhibited PE effects almost completely (from 132+/-3 to 101+/-1%), whereas TER and SAL caused only partial inhibition (from 131+/-2 to 114+/-2 and 129+/-1 to 111+/-2%, respectively). Pretreatment of cardiomyocytes with PTX (250 ng ml(-1) for 16 h at 37 degrees C) did not affect FEN effects, but converted TER- and SAL-evoked partial inhibition into complete inhibition. Inhibitory effects of the three beta2-AR agonists were markedly attenuated by beta1-AR selective antagonist CGP 20712A (CGP) (300 nM); in contrast, beta2-AR selective antagonist ICI 118,551 (55 nM) inhibited the inhibitory effects of the three beta2-AR agonists only in PTX-pretreated cardiomyocytes,with beta1-AR blocked by CGP. We conclude that, in adult rat ventricular cardiomyocytes, FEN activates selectively the Gs protein-pathway, while TER and SAL activate the Gs- and Gi-protein pathways. Part of the effects of these three beta2-AR agonists appears to be mediated by beta1-AR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic beta-2 Receptor Agonists*
  • Adrenergic beta-Agonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology
  • Albuterol / pharmacology
  • Animals
  • Cells, Cultured
  • Fenoterol / pharmacology
  • GTP-Binding Protein alpha Subunits, Gi-Go / agonists*
  • GTP-Binding Protein alpha Subunits, Gs / physiology*
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Kinetics
  • Male
  • Muscle Proteins / biosynthesis
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Pertussis Toxin / pharmacology
  • Phenylalanine / metabolism
  • Phenylephrine / antagonists & inhibitors
  • Phenylephrine / pharmacology
  • Propanolamines / pharmacology
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Terbutaline / pharmacology


  • Adrenergic alpha-Agonists
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Imidazoles
  • Muscle Proteins
  • Propanolamines
  • Phenylephrine
  • Fenoterol
  • ICI 118551
  • Phenylalanine
  • CGP 20712A
  • Pertussis Toxin
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gs
  • Terbutaline
  • Albuterol