Comparative pharmacology of human β-adrenergic receptor subtypes—characterization of stably transfected receptors in CHO cells

  title={Comparative pharmacology of human $\beta$-adrenergic receptor subtypes—characterization of stably transfected receptors in CHO cells},
  author={Carsten Hoffmann and Manfred Leitz and Silke U. Oberdorf‐Maass and Martin J. Lohse and Karl-Norbert Klotz},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
Although many β1-receptor antagonists and β2-receptor agonists have been used in pharmacotherapy for many years their pharmacological properties at all three known subtypes of β-adrenergic receptors are not always well characterized. The aim of this study was, therefore, to provide comparative binding characteristics of agonists (epinephrine, norepinephrine, isoproterenol, fenoterol, salbutamol, salmeterol, terbutalin, formoterol, broxaterol) and antagonists (propranolol, alprenolol, atenolol… 

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.

Evidence for a Secondary State of the Human β3-Adrenoceptor

  • J. Baker
  • Biology, Chemistry
    Molecular Pharmacology
  • 2005
The pharmacology of the human β3-adrenoceptor stably expressed in Chinese hamster ovary cells is examined to suggest that it exists in at least two different agonist conformations with a similar high- and low-affinity pharmacology analogous to, if not as pronounced as, the β1-adRenoceptor.

Pharmacologic Characterization of the Cloned Human Trace Amine-Associated Receptor1 (TAAR1) and Evidence for Species Differences with the Rat TAAR1

The TAAR1 receptor exhibits a pharmacologic profile uniquely different from those of classic monoaminergic receptors, consistent with the structural information that places them in a distinct family of receptors, and suggests the potential for development of TAAR-selective agonists and antagonists to study their physiologic roles.

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.

Comparison of three radioligands for the labelling of human β-adrenoceptor subtypes

All three radioligands are ill-suited to label β3-adrenoceptors, particularly in preparations co-expressing multiple subtypes, and in the absence of alternatives, [125I]-cyanopindolol appears the least unsuitable.

The selectivity of β‐adrenoceptor antagonists at the human β1, β2 and β3 adrenoceptors

This study shows that the β1/β2 selectivity of most clinically used β‐blockers is poor in intact cells, and that some compounds that are traditionally classed as ‘β1‐selective’ actually have higher affinity for the β2‐adrenoceptor.

Desensitization of cAMP Accumulation via Human β3-Adrenoceptors Expressed in Human Embryonic Kidney Cells by Full, Partial, and Biased Agonists

It is concluded that a minor degree of efficacy for cAMP formation may be sufficient to induced full desensitization of that response and to detect ERK phosphorylation despite testing a wide variation of conditions.

Specificity evaluation of antibodies against human β3-adrenoceptors

It is proposed that concordant staining by both antibodies provides the most convincing evidence for β3-adrenoceptor labelling in cyto- or histochemistry studies.

b -Adrenergic Agonists Mediate Enhancement of b 1 -Adrenergic Receptor N-terminal Cleavage and Stabilization In Vivo and In Vitro s

The results underscore the pluridimensionality of b-adrenergic ligands and extend this property from receptor activation and signaling to the regulation of b1AR levels.



Expression of three human beta-adrenergic-receptor subtypes in transfected Chinese hamster ovary cells.

It is likely that the pattern of ligand binding and adenylate cyclase activation, mediated by the new beta 3 AR in CHO cells, also reflects the yet-undetermined pharmacological profile in humans.

Potent and selective human beta(3)-adrenergic receptor antagonists.

Novel and selective beta(3)-AR antagonists with high affinity for the human receptor are described and specific 3'-phenoxy substitutions are described that transform these compounds from potent agonists into selective antagonists.

Expression of a human cDNA encoding the beta 2-adrenergic receptor in Chinese hamster fibroblasts (CHW): functionality and regulation of the expressed receptors.

The data indicate that the expressed human beta 2-AR displays typical functional characteristics of adenylate cyclase-coupled receptors including agonist-induced desensitization, and the availability of this series of cellular clones provides a unique set of biological reagents for future studies of beta2-AR function and regulation.

Stable overexpression of human beta 2-adrenergic receptors in mammalian cells.

  • M. Lohse
  • Biology
    Naunyn-Schmiedeberg's archives of pharmacology
  • 1992
The expression system described here allows the preparation of human beta 2-adrenergic receptors in quantities sufficient for pharmacological and biochemical investigations.

Quantitative analysis of the selectivity of radioligands for subtypes of beta adrenergic receptors.

A method of simultaneous regression analysis of multiple inhibition curves, using the program MLAB on the PROPHET system, was used to quantify the selectivity of radioligands for beta-1 or beta-2 adrenergic receptors.

The Myocardium-protective Gly-49 Variant of the β1-Adrenergic Receptor Exhibits Constitutive Activity and Increased Desensitization and Down-regulation*

The Gly-49-β1AR displayed a more profound agonist-promoted down-regulation than the Ser-49 variant, further supporting the concept that β1AR desensitization is protective in heart failure.

Molecular characterization of the human beta 3-adrenergic receptor.

Novel beta-AR agonists having high thermogenic, antiobesity, and antidiabetic activities in animal models are among the most potent stimulators of the beta 3-AR.

A binding site model and structure-activity relationships for the rat A3 adenosine receptor.

The model presented here, which is consistent with the detailed SAR found in this study, may serve to suggest future chemical modification, site-directed mutagenesis, and SAR studies to further define essential characteristics of the ligand-receptor interaction and to develop even more potent and selective A3 receptor ligands.

The A3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells.

Data indicate that the unique AR that potentiates the secretory response to antigen in RBL-2H3 cells is exclusively the recently cloned A3AR.

Molecular Cloning and Characterization of the Human A_3 Adenosine Receptor

The human A3 adenosine receptor was cloned from a striatal cDNA library using a probe derived from the homologous rat sequence and Antagonist potencies determined by Schild analyses correlated well with those established by competition for radioligand binding.