Involvement of β 3-adrenoceptors in mouse urinary bladder function: Role in detrusor muscle relaxation and micturition reflex

Abstract

β 3-adrenoceptor activation produces relaxation of human urinary bladder smooth muscle (detrusor). Therefore, β 3-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 β 3-adrenoceptors in mouse isolated urinary bladder using the selective β 3-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 (pEC 50 = 6.4 ± 0.4) as well as spontaneous activity (53 ± 7% at 3 µM) and inhibited EFS-induced contractions (pEC 50 = 7.0 ± 0.2) of the detrusor muscle. The β 3-adrenoceptor antagonist SR59230A (1 µM) significantly inhibited the relaxing effects of CL316,243 on basal tone and neurogenic contractions (pA 2 = 7.0 and 7.2, respectively). Another β 3-adrenoceptor antagonist L748,337 (1-10 µM) significantly blocked the CL316,243-evoked inhibition of neurogenic contractions in a concentration-dependent manner (pK B = 6.8), while the selective β 2-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 β 3-adrenoceptor agonist CL316,243 (as well as various β-adrenoceptor antagonists), functional β 3-adrenoceptors appear to be present in mouse urinary bladder.