PURPOSE: We investigated the presence of functional Beta1, Beta2 and Beta3-adrenoceptor in urothelium and detrusor muscle of human bladder through in vitro pharmacology of selective Beta3 adrenoceptor agonist solabegron. MATERIALS AND METHODS: Expression of these adrenoceptors in surgically separated human urothelium and detrusor muscle were investigated using RT-PCR. The effects of activating these receptors were studied by determining the relaxation produced by Beta-adrenoceptors agonist in pre-contracted human detrusor strips. RESULTS: The results confirmed the presence of mRNA for Beta1, Beta2 and Beta3-adrenoceptor in both human urothelium and detrusor. In an in vitro functional bladder assay, Solabegron and other agonists for Beta-adrenoceptors such as procaterol and isoproterenol evoked potent concentration-dependent relaxation of isolated human bladder strips with pD2 values of 8.73 +/- 0.19, 5.08 +/- 0.48 and 6.28 +/- 0.54, respectively. CONCLUSIONS: Selective Beta3-adrenoceptor agonist may be a potential new treatment for the overactive bladder OAB syndrome. Existence of Beta3-adrenoceptor mRNA exists in the urothelium in addition to the detrusor muscle suggest multiple site of actions for the Beta3-adrenoceptor in the lower urinary tract.
PURPOSE: We investigated the presence of functional Beta1, Beta2 and Beta3-adrenoceptor in urothelium and detrusor muscle of human bladder through in vitro pharmacology of selective Beta3 adrenoceptor agonist solabegron. MATERIALS AND METHODS: Expression of these adrenoceptors in surgically separated human urothelium and detrusor muscle were investigated using RT-PCR. The effects of activating these receptors were studied by determining the relaxation produced by Beta-adrenoceptors agonist in pre-contracted human detrusor strips. RESULTS: The results confirmed the presence of mRNA for Beta1, Beta2 and Beta3-adrenoceptor in both human urothelium and detrusor. In an in vitro functional bladder assay, Solabegron and other agonists for Beta-adrenoceptors such as procaterol and isoproterenol evoked potent concentration-dependent relaxation of isolated human bladder strips with pD2 values of 8.73 +/- 0.19, 5.08 +/- 0.48 and 6.28 +/- 0.54, respectively. CONCLUSIONS: Selective Beta3-adrenoceptor agonist may be a potential new treatment for the overactive bladder OAB syndrome. Existence of Beta3-adrenoceptor mRNA exists in the urothelium in addition to the detrusor muscle suggest multiple site of actions for the Beta3-adrenoceptor in the lower urinary tract.
Authors: Susan A Hall; May Yang; Margaret A Gates; William D Steers; Sharon L Tennstedt; John B McKinlay Journal: J Urol Date: 2012-05-15 Impact factor: 7.450
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Authors: Pradeep Tyagi; Phillip P Smith; George A Kuchel; William C de Groat; Lori A Birder; Christopher J Chermansky; Rosalyn M Adam; Vincent Tse; Michael B Chancellor; Naoki Yoshimura Journal: Int Urol Nephrol Date: 2014-09-20 Impact factor: 2.370