(-)-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 EC50, M, of 7.3. The maximum effects of (-)-CGP 12177 amounted to 15% and 11% of the effects of (-)-isoprenaline (400 microM) and of CaCl2 (6.75 mM) respectively. 3. (-)-Bupranolol 1 microM, an antagonist with a pKB of approximately 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 pKB 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.
Kaumann
A J
AJ
Human Pharmacology Laboratory, Babraham Institute, Cambridge.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D002046:Bupranolol / Q000494:pharmacology; D005260:Female; D006325:Heart Atria / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011941:Receptors, Adrenergic; D002046:Bupranolol; D011433:Propranolol; C033394:CGP 12177