Beta-Blocker Selectivity at Cloned Human Beta1- and Beta2-Adrenergic Receptors

  title={Beta-Blocker Selectivity at Cloned Human Beta1- and Beta2-Adrenergic Receptors},
  author={Carol Smith and Milt Teitler},
  journal={Cardiovascular Drugs and Therapy},
Summary. [...] Key Method Bisoprolol, atenolol, propranolol, betaxolol, metoprolol, carvedilol, and ICI 118, 551 were compared for their beta-receptor selectivity using membranes prepared from recombinant cells selectively expressing human beta2 and beta1 receptors. Bisoprolol was found to have the highest selectivity for the beta1 receptor, displaying a beta2//beta1 ratio of 19 (a 19-fold higher affinity for the beta receptor than for the beta2 receptor). Atenolol, metoprolol, and betaxolol displayed lower…Expand
β-Adrenergic Agonists Mediate Enhancement of β1-Adrenergic Receptor N-terminal Cleavage and Stabilization In Vivo and In Vitro
The results underscore the pluridimensionality of β-adrenergic ligands and extend this property from receptor activation and signaling to the regulation of β1AR levels. Expand
Synthesis and in Vitro and in Vivo Characterization of Highly β1-Selective β-Adrenoceptor Partial Agonists
SAR suggests that an extended alkoxyalkoxy side chain, alongside substituents at the meta- or para-positions of the phenylurea, increases ligand affinity and β1-selectivity. Expand
Carvedilol blocks beta2- more than beta1-adrenoceptors in human heart.
Carvedilol blocks human cardiac beta2-adrenoceptors more than beta1- adrenoCEPTors, thereby conceivably contributing to the beneficial effects in heart failure. Expand
Theoretical study on some non-selective beta-adrenergic antagonists and correlation to their biologically active configurations
The non-selective classification refers to those beta-blockers capable of blocking both β1 and β2 receptors with equivalent efficacy. All of these beta-blockers consist of an aryloxypropanolamineExpand
The selectivity of β‐adrenoceptor antagonists at the human β1, β2 and β3 adrenoceptors
1 β‐Adrenoceptor antagonists (‘β‐blockers’) are one of the most widely used classes of drugs in cardiovascular medicine (hypertension, ischaemic heart disease and increasingly in heart failure) asExpand
The selectivity of β‐adrenoceptor agonists at human β1‐, β2‐ and β3‐adrenoceptors
  • J. Baker
  • Medicine
  • British journal of pharmacology
  • 2010
This study examined the affinity and intrinsic efficacy of 31 β‐adrenoceptor agonists at the three human β‐ adrenoceptors to determine whether the current agonists are subtype selective because of affinity or intrinsic efficacy. Expand
Beta 1-adrenoceptor selectivity of nebivolol and bisoprolol. A comparison of [3H]CGP 12.177 and [125I]iodocyanopindolol binding studies.
It is concluded that nebivolol is approximately 3.5 times more beta(1)-adrenoceptor-selective than bisoprolol in the human myocardium and in vivo metabolized nebvolol retains beta( 1)-adRenoceptor selectivity. Expand
Human β 1 -adrenergic receptor : biosynthesis, processing and the carboxyl-terminal polymorphism
The β1-adrenergic receptor (β1AR) belongs to the large family of G protein-coupled receptors. It is activated by epinephrine and norepinephrine and thus has a central role in mediating the effects ofExpand
Cell-based beta2-adrenergic receptor-ligand binding assay using synthesized europium-labeled ligands and time-resolved fluorescence.
High-sensitivity, high-throughput, and user-friendly lanthanide-based assays for receptor-ligand interactions provide an attractive alternative to the traditional radioligand displacement assays. InExpand
Predicting in vivo cardiovascular properties of β-blockers from cellular assays: a quantitative comparison of cellular and cardiovascular pharmacological responses
An excellent correlation was obtained between in vivo and in vitro measures of β1‐adrenoceptor efficacy and predicting in vivo cardiovascular properties of β‐blockers from cellular assays: a quantitative comparison of cellular and cardiovascular pharmacological responses. Expand


Properties of the beta 1- and beta 2-adrenergic receptor subtypes revealed by molecular cloning.
The beta 1- and beta 2-adrenergic receptor subtypes are biochemically and functionally similar, because both receptors mediate the catecholamine-dependent activation of adenylate cyclase through theExpand
Structure and regulation of G protein-coupled receptors: the beta 2-adrenergic receptor as a model.
Publisher Summary This chapter discusses the major findings concerning the structure and coupling properties of G protein-coupled receptors and describes what is currently known about the pathwaysExpand
bisoprolol (emd 33512), a Highly Selective β1-adrenoceptor Antagonist: In Vitro and In Vivo Studies
It is demonstrated in vitro and in vivo that bisoprolol is a selective β1-adrenoceptor antagonist without ISA, possessing low affinity to β2- adrenoceptors, a suitable tool to study β-ad Renin subtypes in the human being. Expand
Cloning of the cDNA and genes for the hamster and human beta 2-adrenergic receptors.
The cloning of the genes and the elucidation of the aa sequences for these G-protein coupled receptors should help to determine the structure-function as well as the evolutionary relationship of these proteins. Expand
Cloning of the cDNA for the human beta 1-adrenergic receptor.
RNA blot analysis indicates a message of 2.5 kilobases in rat tissues, with a pattern of tissue distribution consistent with beta 1AR binding, which suggests that the avian gene encoding beta AR and the human gene encodingbeta 1AR evolved from a common ancestral gene. Expand
Mutagenesis of the beta 2-adrenergic receptor: how structure elucidates function.
The cloning of .B2AR cDNA from hamster, human, rat, and mouse, as well as the gene from human genomic DNA, has allowed us to study the signal transduction pathway initiated by the f32AR and mediated by Gs. Expand
Structure and function of the adrenergic receptor family.
The interaction of hormones and drugs with their respective targets has been widely studied with the hope that a better understanding of the molecular basis of their actions would provide insightsExpand
Catecholamine receptors: structure, function, and regulation.
The various receptors for catecholamines, termed adrenergic receptors, represent excellent model systems for the study of receptor-mediated transmembrane signaling systems because of their ubiquity,Expand
Isoproterenol antagonizes endothelial permeability induced by thrombin and thrombin receptor peptide.
Dose-response experiments demonstrated that isoproterenol antagonized the action of alpha-thrombin and a thrombin receptor peptide on endothelial permeability and that it lowered baseline permeability. Expand
Beta-Blocking Drugs and Coronary Heart Disease
The role of beta-blockers in the treatment of hypertension, angina, acute myocardial infarction, and heart failure is reviewed and the tolerability of these drugs has been questioned, careful examination of clinical trials indicate that they are relatively well tolerated. Expand