Functional Role ofβ3-Adrenoreceptors in the Bladder

The detrusor muscle contains beta-adrenoceptors (beta-AR) and three subtypes, such as beta 1-AR, beta 2-AR, and beta 3-AR, which have been identified in most species. There is a predominant expression of beta 3-AR messenger RNA in human bladder tissue when compared with the beta 1-AR and beta 2-AR subtypes. Moreover, the presence of beta 1, beta 2, and beta 3-AR in the human urothelium has been identified. It has also been demonstrated in animals that relaxation mediated through beta s-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+(BKCa) channels may be involved in beta-adrenergic relaxation. In addition, a recent phase II proof-of-concept study using a novel selective beta 3-adrenoceptor agonist (YM178) has shown clinical efficacy in the treatment of overactive bladder (OAB) symptoms, suggesting that beta 3-AR should be used as a therapeutic target for the treatment of OAB disorders.