Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder.
10.4111/kju.2010.51.12.811
- Author:
Yasuhiko IGAWA
1
;
Naoki AIZAWA
;
Yukio HOMMA
Author Information
1. Department of Continence Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan. yigawa-jua@umin.ac.jp
- Publication Type:In Vitro ; Review ; Clinical Trial
- Keywords:
Adrenergic beta-agonists;
Afferent pathways;
Urinary bladder, overactive
- MeSH:
Adrenergic beta-Agonists;
Afferent Pathways;
Animals;
Catecholamines;
Contracts;
Dioxoles;
Humans;
Models, Animal;
Muscarinic Antagonists;
Nitric Oxide;
Rats;
RNA, Messenger;
Urinary Bladder;
Urinary Bladder, Overactive;
Urothelium
- From:Korean Journal of Urology
2010;51(12):811-818
- CountryRepublic of Korea
- Language:English
-
Abstract:
In the present review article, we present an overview of beta-adrenoceptor (beta-AR) subtype expression at the mRNA and receptor protein levels in the human detrusor, the in vitro and in vivo bladder function of the beta3-AR, the in vivo effect of beta3-AR agonists on detrusor overactivity in animal models, and the available results of clinical trials of beta3-AR agonists for treating overactive bladder (OAB). There is a predominant expression of beta3-AR mRNA in human bladder, constituting 97% of total beta-AR mRNA. Also, functionally, the relaxant response of human detrusor to catecholamines is mainly mediated through the beta3-ARs. Moreover, the presence of beta1-, beta2-, and beta3-AR mRNAs in the urothelium and suburothelial layer of human bladder has been identified. Stimulation of urothelial beta-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 beta3-AR agonist, in rats selectively inhibits mechano-sensitive Adelta-fiber activity of the primary bladder afferents. A number of selective beta3-AR agonists are currently being evaluated in clinical trials for OAB with promising preliminary results. In conclusion, the beta3-AR agonists are the most notable alternative class of agents to antimuscarinics in the pharmacological treatment of OAB. The beta3-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.
