STRUCTURE AND FUNCTION OF THE β3-ADRENERGIC RECEPTOR

Abstract

▪ Abstract  The β3 subtype of adrenaline and noradrenaline receptors has now been extensively characterized at the structural and functional levels. Ligand binding and adenylyl cyclase activation studies helped define a β-adrenergic profile that is quite distinct from that of the β1-and β2-adrenergic receptors, but strongly reminiscent of most of the “atypical” responses reported in earlier pharmacologic studies. Human, other large mammal, and rodent receptors share most of the characteristic β3 properties, although obvious species-specific differences have been identified. Recently, the incidence of a naturally occurring variant of the human β3-adrenergic receptor was shown to be correlated with hereditary obesity in Pima Indians and in Japanese individuals, and in Western obese patients with increased dynamic capacity to add on weight and develop non–insulin-dependent diabetes mellitus (NIDDM). A mild weight increase was also shown to develop in female, but not male, mice in which the β3 receptor gene was disrupted. Taken together, these results now provide a consistent picture of an important role of the β3-adrenoceptor in the regulation of lipid metabolism and as an obvious target for drugs to treat some forms of obesity.