Agonist‐specific activation of the β2‐adrenoceptor/Gs‐protein and β2‐adrenoceptor/Gi‐protein pathway in adult rat ventricular cardiomyocytes

In rat ventricular cardiomyocytes β2‐adrenoceptors (AR) couple to Gs‐ and Gi‐protein, and evidence has accumulated that β2‐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 β2‐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 β2‐AR agonist activates selectively Gs‐ or Gs‐ and Gi‐protein. PE (1 μM) increased the rate of protein synthesis from 100% to 130±2% (n=34). FEN, TER and SAL (1 nM–10 μM) 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°C) did not affect FEN effects, but converted TER‐ and SAL‐evoked partial inhibition into complete inhibition. Inhibitory effects of the three β2‐AR agonists were markedly attenuated by β1‐AR selective antagonist CGP 20712A (CGP) (300 nM); in contrast, β2‐AR selective antagonist ICI 118,551 (55 nM) inhibited the inhibitory effects of the three β2‐AR agonists only in PTX‐pretreated cardiomyocytes, with β1‐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 β2‐AR agonists appears to be mediated by β1‐AR. British Journal of Pharmacology (2006) 147, 714–719. doi:10.1038/sj.bjp.0706674