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Igawa Y, Aizawa N, Homma Y. Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder. Korean J Urol. 2010;51(12):811-8doi: 10.4111/kju.2010.51.12.811.
Igawa, Y., Aizawa, N., & Homma, Y. (2010). Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder. Korean journal of urology, 51(12), 811-8. https://doi.org/10.4111/kju.2010.51.12.811
Igawa, Yasuhiko, et al. "Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder." Korean journal of urology vol. 51,12 (2010): 811-8. doi: https://doi.org/10.4111/kju.2010.51.12.811
Igawa Y, Aizawa N, Homma Y. Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder. Korean J Urol. 2010 Dec;51(12):811-8. doi: 10.4111/kju.2010.51.12.811. Epub 2010 Dec 21. PMID: 21221199; PMCID: PMC3016425.
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Korean J Urol. 2010 Dec;51(12):811-8. doi: 10.4111/kju.2010.51.12.811. Epub 2010 Dec 21.

Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder.

Korean journal of urology

Yasuhiko Igawa, Naoki Aizawa, Yukio Homma

Affiliations

  1. Department of Continence Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.

PMID: 21221199 PMCID: PMC3016425 DOI: 10.4111/kju.2010.51.12.811

Abstract

In the present review article, we present an overview of beta-adrenoceptor (β-AR) subtype expression at the mRNA and receptor protein levels in the human detrusor, the in vitro and in vivo bladder function of the β3-AR, the in vivo effect of β3-AR agonists on detrusor overactivity in animal models, and the available results of clinical trials of β3-AR agonists for treating overactive bladder (OAB). There is a predominant expression of β3-AR mRNA in human bladder, constituting 97% of total β-AR mRNA. Also, functionally, the relaxant response of human detrusor to catecholamines is mainly mediated through the β3-ARs. Moreover, the presence of β1-, β2-, and β3-AR mRNAs in the urothelium and suburothelial layer of human bladder has been identified. Stimulation of urothelial β-ARs results in the release of nitric oxide and an unknown substance inhibiting detrusor contractions from the urothelium. Intravenous application of CL316,243, a selective β3-AR agonist, in rats selectively inhibits mechano-sensitive Aδ-fiber activity of the primary bladder afferents. A number of selective β3-AR agonists are currently being evaluated in clinical trials for OAB with promising preliminary results. In conclusion, the β3-AR agonists are the most notable alternative class of agents to antimuscarinics in the pharmacological treatment of OAB. The β3-AR agonists act to facilitate bladder storage function probably through at least two mechanisms: first, direct inhibition of the detrusor, and second, inhibition of bladder afferent neurotransduction.

Keywords: Adrenergic beta-agonists; Afferent pathways; Urinary bladder, overactive

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