Reinartz Michael T, Kälble Solveig, Wainer Irving W, Seifert Roland
Institute for Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2015 May;388(5):517-24. doi: 10.1007/s00210-015-1086-5. Epub 2015 Jan 31.
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.
G蛋白偶联受体与配体之间的特异性相互作用是下游信号传导的起点。非诺特罗立体异构体已成功用于探究β2肾上腺素能受体（β2AR）的配体特异性激活（功能选择性）（Reinartz等人，2015年）。在本研究中，我们在激动剂和拮抗剂竞争结合试验中使用β2AR-Gsα融合蛋白扩展了非诺特罗立体异构体的药理学特征。在4'-甲氧基-1-萘基非诺特罗的（R,S'）-和（S,S'）-异构体中发现了结合亲和力与效应器效力之间的解离。我们的数据证实了先前关于非诺特罗衍生物的氨基烷基部分对功能选择性重要性的研究。
