Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder
Korean Journal of Urology
;
: 811-818, 2010.
Article
Dans Anglais
| 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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Vessie urinaire
/
ARN messager
/
Catécholamines
/
Voies afférentes
/
Agonistes bêta-adrénergiques
/
Antagonistes muscariniques
/
Urothélium
/
Modèles animaux
/
Contrats
/
Dioxoles
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Korean Journal of Urology
Année:
2010
Type:
Article
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