STRUCTURE AND FUNCTION OF THE BETA(3)-ADRENERGIC RECEPTOR

The beta(3) 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 beta-adrenergic profile that is quite distinct from that of the bet a(1)-and beta(2)-adrenergic receptors, but strongly reminiscent of mos t of the ''atypical'' responses reported in earlier pharmacologic stud ies. Human, other large mammal, and rodent receptors share most of the characteristic beta(3) properties, although obvious species-specific differences have been identified. Recently, the incidence of a natural ly occurring variant of the human beta(3)-adrenergic receptor was show n to be correlated with hereditary obesity in Pima Indians and in Japa nese 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 beta(3) receptor gene was disr upted. Taken together, these results now provide a consistent picture of an important role of the beta(3)-adrenoceptor in the regulation of lipid metabolism and as an obvious target for drugs to treat some form s of obesity.