(—)‐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 β₃-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.