Involvement of β3-adrenoceptors in mouse urinary bladder function: Role in detrusor muscle relaxation and micturition reflex

β3-adrenoceptor activation produces relaxation of human urinary bladder smooth muscle (detrusor). Therefore, β3-adrenoceptor agonism is being investigated as a new therapeutic strategy for the treatment of overactive bladder. The aim of the current study was to identify the functional presence of β3-adrenoceptors in mouse isolated urinary bladder using the selective β3-adrenoceptor agonist CL316,243 and antagonists SR59230A and L748,337. The effects of CL316,243 on basal tone, spontaneous activity and electrical field stimulation (EFS)-induced contractions were investigated using in vitro techniques, while the in vivo effects of intravenously administered CL316,243 on the micturition reflex were investigated using cystometry. CL316,243 decreased basal tone (pEC50 = 6.4 ± 0.4) as well as spontaneous activity (53 ± 7% at 3 µM) and inhibited EFS-induced contractions (pEC50 = 7.0 ± 0.2) of the detrusor muscle. The β3-adrenoceptor antagonist SR59230A (1 µM) significantly inhibited the relaxing effects of CL316,243 on basal tone and neurogenic contractions (pA2 = 7.0 and 7.2, respectively). Another β3-adrenoceptor antagonist L748,337 (1-10 µM) significantly blocked the CL316,243-evoked inhibition of neurogenic contractions in a concentration-dependent manner (pKB = 6.8), while the selective β2-adrenoceptor antagonist ICI118,551(30 nM) had no effect. In anesthetized mice, CL316,243 (0.03 and 0.1 mg/kg, i.v.) significantly increased bladder capacity and threshold pressure without a modification of bladder compliance. Moreover, it induced a significant decrease in the amplitude of both micturition and non-voiding contractions. Based on the current results obtained using the β3-adrenoceptor agonist CL316,243 (as well as various β-adrenoceptor antagonists), functional β3-adrenoceptors appear to be present in mouse urinary bladder.