Molecular Characterization of the Human β ₃ -Adrenergic Receptor

TLDR

β‑adrenergic receptors were originally classified into β1 and β2 subtypes, but additional β‑ARs have been implicated in regulating metabolic processes via catecholamines. A human β3‑adrenergic receptor gene was isolated, and its expression in cells induced cAMP accumulation upon adrenaline or noradrenaline exposure, with only two classical β‑AR blockers inhibiting this effect while two others acted as β3‑AR agonists, and the agonist potency order matched their ability to stimulate metabolic processes in tissues with atypical adrenergic sites.

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.