Functional Role of β3-Adrenoreceptors in the Bladder

The detrusor muscle contains β-adrenoceptors (β-AR) and three subtypes, such as β1-AR, β2-AR, and β3-AR, which have been identified in most species. There is a predominant expression of β3-AR messenger RNA in human bladder tissue when compared with the β1-AR and β2-AR subtypes. Moreover, the presence of β1, β2, and β3-AR in the human urothelium has been identified. It has also been demonstrated in animals that relaxation mediated through βs-AR is achieved solely by cAMP-dependent mechanisms in non-contracted detrusor muscles, whereas in KCl precontracted detrusor muscles, cAMP-dependent and -independent mechanisms by way of calcium-activated K +(BK Ca) channels may be involved in β-adrenergic relaxation. In addition, a recent phase II proof-of-concept study using a novel selective β3-adrenoceptor agonist (YM178) has shown clinical efficacy in the treatment of overactive bladder (OAB) symptoms, suggesting that β3-AR should be used as a therapeutic target for the treatment of OAB disorders.