Human myocardial beta-adrenoceptors: demonstration of both beta 1- and beta 2-adrenoceptors mediating contractile responses to beta-agonists on the isolated right atrium.
On the isolated electrically driven muscle strip of human right atrial appendages the beta-adrenoceptor subtypes mediating the positive inotropic effects of isoprenaline, dobutamine and procaterol were characterized using the beta 1-selective antagonist bisoprolol and the beta 2-selective antagonist ICI 118,551. The three agonists induced concentration-dependent increases in force of contraction with an order of potency: procaterol (pD2-value: 8.03) greater than isoprenaline (pD2-value: 7.73) greater than dobutamine (pD2-value: 5.44). In saturating concentrations all three agonists produced the same maximum of developed tension. ICI 118,551 (10(-9)--10(-7) mol/l) and bisoprolol (10(-9)--10(-7) mol/l) were nearly equipotent in antagonizing the positive inotropic effects of isoprenaline and dobutamine. However, the slopes of the Schild-plots for both antagonists against both agonists were significantly less than 1.0 indicating interaction with beta 1- and beta 2-adrenoceptors. On the other hand, ICI 118,551 (10(-10)--10(-8) mol/l) was approximately 100 times more potent than bisoprolol (10(-8)--10(-6) mol/l) in antagonizing the positive inotropic effect of the highly selective beta 2-agonist procaterol. In addition, the slopes of the Schild-plots for antagonism of ICI 118,551 and bisoprolol against procaterol were not significantly different from unity indicating interaction with a homogeneous class of beta-adrenoceptors. The pA2-value for ICI 118,551 was 9.49, for bisoprolol it amounted to 6.99.(ABSTRACT TRUNCATED AT 250 WORDS)
Zerkowski
H R
HR
Ikezono
K
K
Rohm
N
N
Reidemeister
J C
JC
Brodde
O E
OE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D017298:Bisoprolol; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D017265:Procaterol; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; C026777:ICI 118551; D007545:Isoproterenol; D017265:Procaterol; D017298:Bisoprolol