Human myocardial ?-adrenoceptors: demonstration of both ?-adrenoceptors: mediating contractile responses to ?-agonists on the isolated right atrium

Abstract

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)

The Effect of Diabetes on Expression of β1-,β2-, and β3-Adrenoreceptors in Rat Hearts

“…In a recent study, we demonstrated that ␤ 1 -AR-mediated chronotropic responses in right atria of STZ-induced diabetic rats are impaired, but those mediated via ␤ 2 -ARs are preserved (9). It has also been demonstrated that in the human atrium, both ␤ 1 -and ␤ 2 -ARs are functionally coupled to the adenylate cyclase system (10), and both subtypes of ␤-ARs are reported to contribute to the cardiac responses of ␤-AR agonists (11). Thus it has been suggested that, in the human right atrium, both ␤ 1 -and ␤ 2 -ARs are involved in the physiological regulation of the force of contraction and/or heart rate.…”

“…In those studies, however, ␤-ARs were not differentiated according to their subtypes. ␤-ARs of both the ␤ 1 and ␤ 2 subtypes have been reported to coexist in certain cardiac tissues (10,11). Human cardiac ␤ 1 -and ␤ 2 -ARs are coupled to adenylate cyclase through the G s protein.…”

Contribution of β1‐ and β2‐adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (−)‐atenolol

“…As a result the blocking potency of (-)atenolol would be greater against (-)-noradrenaline (mostly acts through f1-adrenoceptors) than against (-)-adrenaline (acts through both #1-and f2-adrenoceptors); this was indeed observed. Evidence with physiological catecholamines (Gille et al, 1985;Kaumann & Lobnig, 1986;Kaumann & Lemoine, 1987) and non-physiological agonists (Mugge et al, 1985;Bristow et al, 1986;Zerkowski et al, 1986) Hall et al (1988). They observed that (-)-adrenaline (but not (-)-noradrenaline) was a more potent inotropic stimulant on atria from (-)atenolol-treated than on those from untreated patients and that the enhanced responses were not affected by selective blockade of fi1-adrenoceptors but eliminated by selective blockade of #2-adrenoceptors.…”

Effects of chronic intravenous infusions of dopexamine and isoprenaline to rats on D1‐, β1‐ and β2‐receptor‐mediated responses

“…Additionally, some inotropic support is provided by direct stimulation of cardiac P2-adrenoceptors, by activation of reflex mechanisms arising from the vasodepressor action and by inhibition of uptake, which results in potentiation of the action of noradrenaline on P,-adrenoceptors (Smith & O'Connor, 1988). Although PI-adrenoceptors predominate over P2-adrenoceptors in the human heart (Bristow et al, 1986;Bohm et al, 1989;Brodde et al, 1989;Steinfath et al, 1991), the smaller P2-adrenoceptor population which also mediates contractile responses (Ablad et al, 1974;Zerkowski et al, 1986) may become more important in some forms of heart disease.…”