Involvement of beta(3)-adrenoceptors in mouse urinary bladder function: role in detrusor muscle relaxation and micturition reflex

• Published in: European journal of pharmacology 2009-09, Vol.618 (1-3), p.76-83
• Main Authors: Deba, Aurore, Palea, Stefano, Rouget, Celine, Westfall, Timothy D, Lluel, Philippe
• Format: Article
• Language: English
• Subjects: Adrenergic beta-3 Receptor Agonists; Adrenergic beta-3 Receptor Antagonists; Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animals; Dioxoles - pharmacology; Electric Stimulation; Female; In Vitro Techniques; Mice; Mice, Inbred C57BL; Muscle Relaxation - drug effects; Muscles - drug effects; Muscles - innervation; Muscles - metabolism; Muscles - physiology; Receptors, Adrenergic, beta-3 - metabolism; Reflex - drug effects; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Urinary Bladder - physiology; Urination - drug effects
• ISSN: 1879-0712
• DOI: 10.1016/j.ejphar.2009.07.012

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