Beta-adrenoceptor-binding studies of the cardioselective beta blockers bisoprolol, H-I 42 BS, and HX-CH 44 BS to heart membranes and intact ventricular myocytes of adult rats: two beta 1-binding sites for bisoprolol.
beta-Adrenoceptor binding of cardioselective drugs to intact ventricular myocytes was performed using [3H]CGP-12177, a hydrophilic non-beta 1/beta 2-selective antagonist radioligand. The beta-adrenoceptor density on the intact cardiomyocytes was about 2 x 10(5) molecules/cell. The beta 1-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 beta 1-antagonists bind in a biphasic manner with about 30% of an additional low affinity site, presumably corresponding to the beta 2-adrenoceptor. The beta 1-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 beta 1-adrenoceptor binding sites exhibiting different affinities for bisoprolol, whereas beta 2-adrenergic receptors are completely absent.
Department of Pharmacological Research, Thomae Research Laboratory, Biberach/Riss, F.R.G.
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Mauz
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Pelzer
D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D017298:Bisoprolol; D002462:Cell Membrane / Q000378:metabolism; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011412:Propanolamines / Q000378:metabolism*; D011433:Propranolol / Q000378:metabolism; D052999:Quinazolinones; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D007546:Isoquinolines; D011412:Propanolamines; D052999:Quinazolinones; D011943:Receptors, Adrenergic, beta; C045062:HI 42; C045066:HX-CH 44BS; D011433:Propranolol; C033394:CGP 12177; D017298:Bisoprolol