Direct Labelling of Myocardial Beta 1-adrenoceptors. Comparison of Binding Affinity of 3H-(-)-bisoprolol with Its Blocking Potency

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1985 Oct 1

PMID 2866449

Citations 22

Authors

A J Kaumann

H Lemoine

Affiliations

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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)

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Stimulant and blocking effects of optical isomers of pindolol on the sinoatrial node and trachea of guinea pig. Role of beta-adrenoceptor subtypes in the dissociation between blockade and stimulation.

Walter M, Lemoine H, Kaumann A Naunyn Schmiedebergs Arch Pharmacol. 1984; 327(2):159-75.

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References

Gille E, Lemoine H, Ehle B, Kaumann A . The affinity of (-)-propranolol for beta 1- and beta 2-adrenoceptors of human heart. Differential antagonism of the positive inotropic effects and adenylate cyclase stimulation by (-)-noradrenaline and (-)-adrenaline. Naunyn Schmiedebergs Arch Pharmacol. 1985; 331(1):60-70. DOI: 10.1007/BF00498852. View

Ehle B, Lemoine H, Kaumann A . Improved evaluation of binding of ligands to membranes containing several receptor-subtypes. Naunyn Schmiedebergs Arch Pharmacol. 1985; 331(1):52-9. DOI: 10.1007/BF00498851. View

Moustafa E, Giachetti A, Downey H, BASHOUR F . Binding of (3H)dihydroalprenolol to beta adrenoceptors of cells isolated from adult rat heart. Naunyn Schmiedebergs Arch Pharmacol. 1978; 303(1):107-9. DOI: 10.1007/BF00496192. View

Lemoine H, Kaumann A . A model for the interaction of competitive antagonists with two receptor-subtypes characterized by a Schild-plot with apparent slope unity. Agonist-dependent enantiomeric affinity ratios for bupranolol in tracheae but not in right atria of guinea.... Naunyn Schmiedebergs Arch Pharmacol. 1983; 322(2):111-20. DOI: 10.1007/BF00512383. View

Kaumann A, Marano M . On equilibrium dissociation constants for complexes of drug-receptor subtypes. Selective and non-selective interactions of partial agonists with two plausible beta-adrenoceptor subtypes mediating positive chronotropic effects of (-)-isoprenaline in.... Naunyn Schmiedebergs Arch Pharmacol. 1982; 318(3):192-201. DOI: 10.1007/BF00500480. View

Morris T, Kaumann A . Different steric characteristics of beta 1- and beta 2-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1984; 327(2):176-9. DOI: 10.1007/BF00500913. View

Morris T, Sandrock K, Kaumann A . 3H-(-)-Bupranolol, a new beta-adrenoceptor radioligand: characterization of its binding to kitten heart beta-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1981; 317(1):19-25. DOI: 10.1007/BF00506251. View

ARUNLAKSHANA O, SCHILD H . Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959; 14(1):48-58. PMC: 1481829. DOI: 10.1111/j.1476-5381.1959.tb00928.x. View

Kaumann A . Potentiation of the effects of isoprenaline and noradrenaline by hydrocortisone in cat heart muscle. Naunyn Schmiedebergs Arch Pharmacol. 1972; 273(1):134-53. DOI: 10.1007/BF00508086. View

10.

Manalan A, Besch Jr H, Watanabe A . Characterization of [3H](+/-)carazolol binding to beta-adrenergic receptors. Application to study of beta-adrenergic receptor subtypes in canine ventricular myocardium and lung. Circ Res. 1981; 49(2):326-36. DOI: 10.1161/01.res.49.2.326. View

11.

Walter M, Lemoine H, Kaumann A . Stimulant and blocking effects of optical isomers of pindolol on the sinoatrial node and trachea of guinea pig. Role of beta-adrenoceptor subtypes in the dissociation between blockade and stimulation. Naunyn Schmiedebergs Arch Pharmacol. 1984; 327(2):159-75. DOI: 10.1007/BF00500912. View

12.

Lemoine H, Ehle B, Kaumann A . Direct labelling of beta 2-adrenoceptors. Comparison of binding potency of 3H-ICI 118,551 and blocking potency of ICI 118,551. Naunyn Schmiedebergs Arch Pharmacol. 1985; 331(1):40-51. DOI: 10.1007/BF00498850. View

13.

Hellenbrecht D, Lemmer B, Wiethold G, Grobecker H . Measurement of hydrophobicity, surface activity, local anaesthesia, and myocardial conduction velocity as quantitative parameters of the non-specific membrane affinity of nine -adrenergic blocking agents. Naunyn Schmiedebergs Arch Pharmacol. 1973; 277(2):211-26. DOI: 10.1007/BF00501161. View

14.

Kaumann A, Lemoine H, Morris T, Schwederski U . An initial characterization of human heart beta-adrenoceptors and their mediation of the positive inotropic effects of catecholamines. Naunyn Schmiedebergs Arch Pharmacol. 1982; 319(3):216-21. DOI: 10.1007/BF00495868. View

15.

Minneman K, Pittman R, Molinoff P . Beta-adrenergic receptor subtypes: properties, distribution, and regulation. Annu Rev Neurosci. 1981; 4:419-61. DOI: 10.1146/annurev.ne.04.030181.002223. View

16.

Minneman K, Hegstrand L, Molinoff P . Simultaneous determination of beta-1 and beta-2-adrenergic receptors in tissues containing both receptor subtypes. Mol Pharmacol. 1979; 16(1):34-46. View

17.

Wachter W, Munch U, Lemoine H, Kaumann A . Evidence that (+)-bupranolol interacts directly with myocardial beta-adrenoceptors. Control of optical purity with differential thermal analysis. Naunyn Schmiedebergs Arch Pharmacol. 1980; 313(1):1-8. DOI: 10.1007/BF00505796. View

18.

BLINKS J . Convenient apparatus for recording contractions of isolated heart muscle. J Appl Physiol. 1965; 20(4):755-7. DOI: 10.1152/jappl.1965.20.4.755. View

19.

Kaumann A . On spare beta-adrenoceptors of inotropic effect of catecholamines in kitten ventricle. Naunyn Schmiedebergs Arch Pharmacol. 1978; 305(2):97-102. DOI: 10.1007/BF00508277. View

20.

Lefkowitz R, Stadel J, Caron M . Adenylate cyclase-coupled beta-adrenergic receptors: structure and mechanisms of activation and desensitization. Annu Rev Biochem. 1983; 52:159-86. DOI: 10.1146/annurev.bi.52.070183.001111. View