β-Adrenoceptor-Binding Studies of the Cardioselective β Blockers Bisoprolol, H-I 42 BS, and HX-CH 44 BS to Heart Membranes and Intact Ventricular Myocytes of Adult Rats

Abstract

β-Adrenoceptor binding of cardioselective drugs to intact ventricular myocytes was performed using [3H]CGP-12177, a hydrophilic non-β1/β2-selective antagonist radioligand. The β-adrenoceptor density on the intact cardiomyocytes was about 2 ± 105 molecules/cell. The β1,-selective antagonists H-I 42 BS and HX-CH 44 BS competed for [3H]CGP-12177 binding sites on the ventricular myocytes in an essentially monophasic manner with Ki = 72.6 nM and Ki = 76.7 nM. respectively. This is in contrast to the results of binding data from heart membranes, where these β1-antagonists bind in a biphasic manner with about 30% of an additional low affinity site, presumably corresponding to the β2-adrenoceptor. The β1-selective antagonist bisoprolol revealed two binding sites at the heart membranes and at the myocytes as well with Ki(1)= 34.2 and 20.0 nM and Ki(2) = 3.014 and 918 nM, respectively. Our results suggest that viable adult rat ventricular myocytes may contain two β1-adrenoceptor binding sites exhibiting different affinities for bisoprolol, whereas β2-adrenergic receptors are completely absent.