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

1 The inotropic effects of (-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one ((-)-CGP 12177), an antagonist for beta(1)- and beta(2)-adrenoceptors as well as an agonist for beta(3)-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 EC(50), M, of 7.3. The maximum effects of(-)-CGP 12177 amounted to 15% and 11% of the effects of (-)-isoprenaline (400 mu M) and of CaCl2 (6.75 mM) respectively. 3 (-)-Bupranolol 1 mu M, an antagonist with a pK(B) of similar to 7.5 for beta(3)-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 beta-adrenoceptor population, possibly related to beta(3)-adrenoceptors.