Adrenoceptor beta-3 (ADRB3)

Adrenoceptor beta-3 (ADRB3) is a member of the G protein-coupled receptor family primarily expressed in the urinary bladder detrusor muscle, adipose tissue, and the heart [1, 4, 20]. In the bladder, ADRB3 activation mediates smooth muscle relaxation, facilitating urine storage and serving as the primary mechanism for treating overactive bladder syndrome [6, 9]. In adipose tissue, the receptor plays a critical role in metabolic regulation by stimulating lipolysis in white fat and thermogenesis in brown/beige fat through the activation of the cAMP-PKA pathway [2, 21]. Beyond its metabolic and urological roles, ADRB3 is increasingly recognized for its cardioprotective functions, where it acts as a physiological 'brake' to counteract excessive catecholamine-induced stress by promoting vasodilation and negative inotropy via nitric oxide production [18, 19]. A notable feature of ADRB3 is its relative resistance to desensitization compared to beta-1 and beta-2 receptors, making it an attractive target for chronic therapeutic interventions [7, 20]. While it is a validated target for urinary incontinence, ongoing research continues to explore its potential in metabolic syndrome, heart failure, and cancer progression [8, 12, 20].

Other names

Beta-3 adrenergic receptorBETA3ARBeta-3 adrenoceptorBeta-3 adrenoreceptor

Selective agonism of the Adrenoceptor beta-3 stimulates Gs protein-mediated activation of adenylate cyclase, leading to increased intracellular cyclic AMP (cAMP) levels [6, 7]. This signaling pathway promotes the relaxation of the detrusor smooth muscle in the bladder to increase storage capacity and regulates energy expenditure by inducing lipolysis and thermogenesis in adipose tissue [1, 3, 21]. In the heart, it can also couple with Gi proteins to exert a negative inotropic effect, acting as a physiological brake against sympathetic overstimulation, and may stimulate nitric oxide release to promote vasodilation [6, 18].