Key result
In isolated human right atrial appendages, (-)-CGP 12177 increased contractile force with a -log EC50 of 7.3, consistent with a putative third beta-adrenoceptor population.
Why the study?
Does (-)-CGP 12177 increase contractile force in human atrial myocardium through a putative third beta-adrenoceptor?
Does (-)-CGP 12177 increase contractile force in human atrial myocardium through a putative third beta-adrenoceptor?
Effect estimate: -log EC50 7.3
The positive inotropic effects of (-)-CGP 12177 in human atrial myocardium, resistant to propranolol but antagonized by bupranolol, suggest the existence of a third beta-adrenoceptor population, possibly beta-3.
Suggests propranolol-resistant inotropy in human atrium; leaves open in vivo role and therapeutic relevance of a putative third beta-adrenoceptor.
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.
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Alberto J. Kaumann (1996) studied Patients without advanced heart failure undergoing open heart surgery. (-)-CGP 12177 vs. (-)-isoprenaline and CaCl2 was evaluated on Contractile force (-log EC50 7.3). In isolated human right atrial appendages, (-)-CGP 12177 increased contractile force with a -log EC50 of 7.3, consistent with a putative third beta-adrenoceptor population.
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