(-)-CGP 12177-induced increase of human atrial contraction through a putative third β-adrenoceptor

Abstract

1 The inotropic effects of (-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one ((-)-CGP 12177), an antagonist for β1- and β2-adrenoceptors as well as an agonist for β3-adrenoceptors, were investigated on paced preparations of isolated right atrial appendages obtained from patients without advanced heart failure undergoing open heart surgery. 2 In the presence of (-)-propranolol (200 nM), (-)-CGP 12177 increased contractile force with a -log EC50 M, of 7.3. The maximum effects of (-)-CGP 12177 amounted to 15% and 11% of the effects of (-)-isoprenaline (400 μM) and of CaCl2 (6.75 mM) respectively. 3 (-)-Bupranolol 1 μM, an antagonist with a pK(B) of ~ 7.5 for P3-adrenoceptors, antagonized surmountably the positive inotropic effects of (-)-CGP 12177 (in the presence of 200 nM (-)-propranolol) with an apparent pK(B) of 7.3. 4 The potent positive inotropic effects of (-)-CGP 12177 and their resistance to blockade by (-)-propranolol but antagonism by (-)-bupranolol are consistent with the existence in human atrial myocardium of a minor third β-adrenoceptor population, possibly related to β3-adrenoceptors.