title: Direct labelling of myocardial beta 1-adrenoceptors. Comparison of binding affinity of 3H-(-)-bisoprolol with its blocking potency.
abstract: A radioligand that selectively labels beta 1-adrenoceptors, 3H-(-)-bisoprolol (3H-BIS), is introduced. The binding properties of 3H-BIS to membrane particles of kitten heart are compared with the blocking properties of (-)-bisoprolol against stimulant effects of (-)-adrenaline and (-)-noradrenaline in heart preparations of kitten and guinea pig. 1. On kitten heart tissues (-)-bisoprolol antagonized the positive chronotropic and inotropic effects of catecholamines competitively. The effects of (-)-adrenaline were antagonized considerably less by (-)-bisoprolol than the corresponding effects of (-)-noradrenaline on sinoatrial pacemakers. The antagonism was nearly the same against both (-)-adrenaline and (-)-noradrenaline in left atria and papillary muscles. The data were analyzed with a model for 2-receptor subtypes by non-linear regression. Equilibrium dissociation constants KB (mol/l; -log KB = pKB) for a high-affinity beta 1-adrenoceptor of 8.8 and for a low-affinity beta 2-adrenoceptor of 7.0 were estimated in the three classes of tissues. In kitten sinoatrial pacemaker beta 1-adrenoceptors contribute 76% to the stimulus induced by (-)-adrenaline and 97% to the stimulus induced by (-)-noradrenaline. In ventricle and left atrium beta 1-adrenoceptors contribute 97-99% and 100% to the stimulus caused by (-)-adrenaline and (-)-noradrenaline, respectively. 2. Both 3H-BIS and unlabelled (-)-bisoprolol caused competitive blockade of the positive chronotropic effects of (-)-noradrenaline in guinea-pig right atria. pKB-values of 8.7 were estimated for both unlabelled and tritiated (-)-bisoprolol. The positive chronotropic effects of (-)-adrenaline were antagonized considerably less by (-)-bisoprolol than those of (-)-noradrenaline in guinea-pig atria. In the presence of low concentrations of beta 2-selective ICI 118,551, which did not antagonize beta 1-adrenoceptor mediated effects, (-)-bisoprolol antagonized positive chronotropic effects of (-)-adrenaline to the same extent as those of (-)-noradrenaline. The results are consistent with the concept of a significant role of sinoatrial beta 2-adrenoceptors of guinea pig for the effects of (-)-adrenaline but not for those of (-)-noradrenaline. 3. 3H-BIS associated and dissociated quickly with and from ventricular beta 1-adrenoceptors. A koff of 1.0 min-1 was estimated. An equilibrium dissociation constant pKL* of 8.2 for 3H-BIS was estimated from saturation binding.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.forename: A J
authors.initials: AJ
authors.lastname: Kaumann
authors.forename: H
authors.initials: H
authors.lastname: Lemoine
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D017298:Bisoprolol; D002395:Catecholamines / Q000494:pharmacology; D002415:Cats; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012849:Sinoatrial Node / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D000262:Adenylyl Cyclases; D009638:Norepinephrine; D017298:Bisoprolol; D004837:Epinephrine