Molecular Characterization of the Human β 3 -Adrenergic Receptor

Abstract

Since the classification of β-adrenergic receptors (β-ARs) into β 1 and β 2 subtypes, additional β-ARs have been implicated in the control of various metabolic processes by catecholamines. A human gene has been isolated that encodes a third β-AR, here referred to as the "β 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 β-AR blockers efficiently inhibited this effect, whereas two others behaved as β 3 -AR agonists. The potency order of β-AR agonists for the β 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 β-AR agonists having high thermogenic, antiobesity, and antidiabetic activities in animal models are among the most potent stimulators of the β 3 -AR.