Summary
On the isolated electrically driven muscle strip of human right atrial appendages the β-adrenoceptor subtypes mediating the positive inotropic effects of isoprenaline, dobutamine and procaterol were characterized using the β1-selective antagonist bisoprolol and the β2-selective antagonist ICI 118,551.
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1.
The three agonists induced concentration-dependent increases in force of contraction with an order of potency: procaterol (pD2-value: 8.03) > isoprenaline (pD2-value: 7.73) > dobutamine (pD2-value: 5.44). In saturating concentrations all three agonists produced the same maximum of developed tension.
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2.
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 β1- and β2-adrenoceptors.
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3.
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 β2-adrenoceptors 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 β-adrenoceptors. The pA2-value for ICI 118,551 was 9.49, for bisoprolol it amounted to 6.99.
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4.
These results indicate that on the isolated electrically driven human right atrium isoprenaline and dobutamine produce increases in contractile force via stimulation of β2-adrenoceptors, while the highly selective β2-adrenoceptors procaterol induces its positive inotropic effect predominantly through stimulation of β2-adrenoceptors. It is concluded, therefore, that in human right atrium both β1- and β2-adrenoceptors functionally contribute to the cardiac responses of β-agonists.
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Zerkowski, H.R., Ikezono, K., Rohm, N. et al. Human myocardial β-adrenoceptors: demonstration of both γ-adrenoceptors: mediating contractile responses to β-agonists on the isolated right atrium. Naunyn-Schmiedeberg's Arch. Pharmacol. 332, 142–147 (1986). https://doi.org/10.1007/BF00511404
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DOI: https://doi.org/10.1007/BF00511404