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

@article{Hoffmann2003ComparativePO,
  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},
  year={2003},
  volume={369},
  pages={151-159}
}
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… 

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References

SHOWING 1-10 OF 64 REFERENCES

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

TLDR
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.

TLDR
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.

TLDR
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
TLDR
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.

TLDR
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*

TLDR
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.

TLDR
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.

TLDR
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.

TLDR
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

TLDR
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.
...