Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder
Korean Journal of Urology
;
: 811-818, 2010.
Article
in English
| WPRIM
| ID: wpr-61776
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Urinary Bladder
/
RNA, Messenger
/
Catecholamines
/
Afferent Pathways
/
Adrenergic beta-Agonists
/
Muscarinic Antagonists
/
Urothelium
/
Models, Animal
/
Contracts
/
Dioxoles
Limits:
Animals
/
Humans
Language:
English
Journal:
Korean Journal of Urology
Year:
2010
Type:
Article
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