Emorine L J, Marullo S, Briend-Sutren M M, Patey G, Tate K, Delavier-Klutchko C, Strosberg A D
CNRS, Université Paris VII, France.
Science. 1989 Sep 8;245(4922):1118-21. doi: 10.1126/science.2570461.
Since the classification of beta-adrenergic receptors (beta-ARs) into beta 1 and beta 2 subtypes, additional beta-ARs have been implicated in the control of various metabolic processes by catecholamines. A human gene has been isolated that encodes a third beta-AR, here referred to as the "beta 3-adrenergic receptor." Exposure of eukaryotic cells transfected with this gene to adrenaline or noradrenaline promotes the accumulation of adenosine 3',5'-monophosphate; only 2 of 11 classical beta-AR blockers efficiently inhibited this effect, whereas two others behaved as beta 3-AR agonists. The potency order of beta-AR agonists for the beta 3-AR correlates with their rank order for stimulating various metabolic processes in tissues where atypical adrenergic sites are thought to exist. In particular, 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.
自从将β-肾上腺素能受体（β-ARs）分为β1和β2亚型以来，更多的β-ARs被认为参与了儿茶酚胺对各种代谢过程的调控。现已分离出一种人类基因，它编码第三种β-AR，在此称为“β3-肾上腺素能受体”。用该基因转染的真核细胞暴露于肾上腺素或去甲肾上腺素会促进3',5'-环磷酸腺苷的积累；11种经典β-AR阻滞剂中只有2种能有效抑制这种效应，而另外两种表现为β3-AR激动剂。β-AR激动剂对β3-AR的效价顺序与其在被认为存在非典型肾上腺素能位点的组织中刺激各种代谢过程的排名顺序相关。特别是，在动物模型中具有高热生成、抗肥胖和抗糖尿病活性的新型β-AR激动剂是β3-AR最有效的刺激剂之一。
