ArticleNaunyn-Schmiedeberg's archives of pharmacology2004
Binding of (-)-[3H]-CGP12177 at two sites in recombinant human beta 1-adrenoceptors and interaction with beta-blockers.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- GPCR-A17 MAAP: mapping modulators, agonists, and antagonists to predict the next bioactive target.Journal of cheminformatics · 2025Article
- Adrenoceptors: Receptors, Ligands and Their Clinical Uses, Molecular Pharmacology and Assays.Handbook of experimental pharmacology · 2024Review
- G-Protein-Coupled Receptor and Ion Channel Genes Used by Influenza Virus for Replication.Journal of virology · 2021Article
- Use of a new proximity assay (NanoBRET) to investigate the ligand-binding characteristics of three fluorescent ligands to the humanPharmacology research & perspectives · 2016Article
- Negative cooperativity across β1-adrenoceptor homodimers provides insights into the nature of the secondary low-affinity CGP 12177 β1-adrenoceptor binding conformation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Agonist binding by the β2-adrenergic receptor: an effect of receptor conformation on ligand association-dissociation characteristics.European biophysics journal : EBJ · 2015Article
- Detection of the secondary, low-affinity β1 -adrenoceptor site in living cells using the fluorescent CGP 12177 derivative BODIPY-TMR-CGP.British journal of pharmacology · 2014Article
- Identification of novel RHPS4-derivative ligands with improved toxicological profiles and telomere-targeting activities.Journal of experimental & clinical cancer research : CR · 2014Article
- Identification of key residues in transmembrane 4 responsible for the secondary, low-affinity conformation of the human β1-adrenoceptor.Molecular pharmacology · 2014Article
- β₃-Adrenergic regulation of L-type Ca²⁺ current and force of contraction in human ventricle.The Journal of membrane biology · 2014Article
- The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors.British journal of pharmacology · 2013Article
- On and off-target effects of telomere uncapping G-quadruplex selective ligands based on pentacyclic acridinium salts.Journal of experimental & clinical cancer research : CR · 2013Article
- Chronic activation of the low affinity site of β1-adrenoceptors stimulates haemodynamics but exacerbates pressure-overload cardiac remodelling.British journal of pharmacology · 2013Article
- Thermodynamics and docking of agonists to the β(2)-adrenoceptor determined using [(3)H](R,R')-4-methoxyfenoterol as the marker ligand.Molecular pharmacology · 2012Article
- The design, synthesis and pharmacological characterization of novel β₂-adrenoceptor antagonists.British journal of pharmacology · 2011Article
- Human atrial β(1L)-adrenoceptor but not β₃-adrenoceptor activation increases force and Ca(2+) current at physiological temperature.British journal of pharmacology · 2011Article
- A full pharmacological analysis of the three turkey β-adrenoceptors and comparison with the human β-adrenoceptors.PloS one · 2010Article
- Phosphodiesterases PDE3 and PDE4 jointly control the inotropic effects but not chronotropic effects of (-)-CGP12177 despite PDE4-evoked sinoatrial bradycardia in rat atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2009Article
- Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- beta3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current.The Journal of clinical investigation · 2008Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To verify the hypothesis that the non-conventional partial agonist (-)-CGP12177 binds at two beta(1)-adrenoceptor sites, human beta(1)-adrenoceptors, expressed in CHO cells, were labelled with (-)-[(3)H]-CGP12177. We compared the binding affinity and antagonist potency of 12 clinically used beta-blockers against the cyclic AMP-enhancing effects of (-)-isoprenaline and (-)-CGP12177.(-)-[(3)H]-CGP12177 bound to a high affinity site (H; K(H)=0.47 nM) and low affinity site (L); K(L)=235 nM). (-)-[(3)H]-CGP12177 dissociated from the beta(1)-adrenoceptors with a fast component (k(off)=0.45 min(-1)), consistent with the L-site, and a slow component (k(off)=0.017-0.033 min(-1)), consistent with the H-site. (-)-Isoprenaline and (-)-CGP12177 caused 96-fold and 12-fold maximal increases in cyclic AMP levels with -logEC(50)M of 8.2 and 7.6. (-)-CGP12177 antagonised the effects of (-)-isoprenaline with a pK(B) of 9.9. The beta-blockers antagonised the effects of (-)-isoprenaline more than the effects of (-)-CGP12177 with potency ratios: (-)-atenolol 1,000, (+/-)-metropolol 676, (-)-pindolol 631, (-)-timolol 589, (+/-)-carvedilol 204, (+/-)-oxprenolol 138, (+/-)-sotalol 132, (-)-propranolol 120, (+/-)-bisoprolol 95, (+/-)-alprenolol 81, (+/-)-nadolol 68 and (-)-bupranolol 56. In intact cells the binding constants of beta-blockers, estimated from competition with 3-5 nM (-)-[(3)H]-CGP12177 (binding to the H-site), correlated with the corresponding affinities estimated from antagonism of the (-)-isoprenaline effects. We conclude that (-)-[(3)H]-CGP12177 binds at two sites in the recombinant beta(1)-adrenoceptor. (-)-CGP12177 is an antagonist of catecholamine effects through the H-site and a non-conventional partial agonist through the L-site. beta-blockers are more potent antagonists through the H-site than the L-site.
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