KMID : 0358320100510120811
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Korean Journal of Urology 2010 Volume.51 No. 12 p.811 ~ p.818
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Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder
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Igawa Yasuhiko
Aizawa Naoki Homma Yukio
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Abstract
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In the present review article, we present an overview of beta-adrenoceptor (¥â-AR) subtype expression at the mRNA and receptor protein levels in the human detrusor, the in vitro and in vivo bladder function of the ¥â3-AR, the in vivo effect of ¥â3-AR agonists on detrusor overactivity in animal models, and the available results of clinical trials of ¥â3-AR agonists for treating overactive bladder (OAB). There is a predominant expression of ¥â3-AR mRNA in human bladder, constituting 97% of total ¥â-AR mRNA. Also, functionally, the relaxant response of human detrusor to catecholamines is mainly mediated through the ¥â3-ARs. Moreover, the presence of ¥â1-, ¥â2-, and ¥â3-AR mRNAs in the urothelium and suburothelial layer of human bladder has been identified. Stimulation of urothelial ¥â-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 ¥â3-AR agonist, in rats selectively inhibits mechano-sensitive A¥ä-fiber activity of the primary bladder afferents. A number of selective ¥â3-AR agonists are currently being evaluated in clinical trials for OAB with promising preliminary results. In conclusion, the ¥â3-AR agonists are the most notable alternative class of agents to antimuscarinics in the pharmacological treatment of OAB. The ¥â3-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.
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KEYWORD
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Adrenergic beta-agonists, Afferent pathways, Urinary bladder, overactive
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