Investigations into the presence of functional Beta1, Beta2 and Beta3-adrenoceptors in urothelium and detrusor of human bladder

Pradeep Tyagi, Catherine A Thomas, Naoki Yoshimura, Michael B Chancellor, Pradeep Tyagi, Catherine A Thomas, Naoki Yoshimura, Michael B Chancellor

Abstract

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.

Source: PubMed

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