title: Interaction of fenoterol stereoisomers with β2-adrenoceptor-G sα fusion proteins: antagonist and agonist competition binding.
abstract: The specific interaction between G-protein-coupled receptors and ligand is the starting point for downstream signaling. Fenoterol stereoisomers were successfully used to probe ligand-specific activation (functional selectivity) of the β2-adrenoceptor (β2AR) (Reinartz et al. 2015). In the present study, we extended the pharmacological profile of fenoterol stereoisomers using β2AR-Gsα fusion proteins in agonist and antagonist competition binding assays. Dissociations between binding affinities and effector potencies were found for (R,S')- and (S,S')-isomers of 4'-methoxy-1-naphthyl-fenoterol. Our data corroborate former studies on the importance of the aminoalkyl moiety of fenoterol derivatives for functional selectivity.
authors: Institute for Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors: Michael T
authors: MT
authors: Reinartz
authors: Solveig
authors: S
authors: Kälble
authors: Irving W
authors: IW
authors: Wainer
authors: Roland
authors: R
authors: Seifert
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology*; D058672:Adrenergic beta-2 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001667:Binding, Competitive; D005280:Fenoterol / Q000031:analogs & derivatives / Q000494:pharmacology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D015394:Molecular Structure; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D061987:Sf9 Cells; D018411:Spodoptera; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D008024:Ligands; D018343:Receptors, Adrenergic, beta-2; D011993:Recombinant Fusion Proteins; D005280:Fenoterol; D019205:GTP-Binding Protein alpha Subunits, Gs
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