title: β-adrenoceptor agonist effects in experimental models of bladder dysfunction.
abstract: β-adrenoceptor stimulation can enhance the storage function of the urinary bladder by acting on detrusor smooth muscle tone, mediator release from the urothelium and/or afferent nerve activity. In humans this may occur predominantly if not exclusively via the β₃-subtype. The effects of β-adrenoceptor agonists including several β₃-selective agonists have been studied in vitro and in vivo, in healthy animals of both genders and various age groups and in a wide range of animal (mostly rat) models of genetic or acquired bladder dysfunction. Such models included bladder irritation by intravesical instillation of acetic acid or prostaglandin E₂, bladder outlet obstruction, stroke, diabetes, spontaneously hypertensive rats, and NO synthase inhibition. Across all of these models β-adrenoceptor agonists had effects consistent with improved bladder storage function. β₃-adrenoceptor effects are resistant to agonist-induced desensitization in many cell types, but whether this also applies to the human bladder is unknown. The efficacy of β-adrenoceptor agonists appears to be largely unaffected by common polymorphisms of the β₃-adrenoceptor gene. Taken together these findings suggest that β₃-adrenoceptor agonists may become useful drugs for the treatment of bladder storage dysfunction, a view supported by recent phase III clinical studies for one such agent, mirabegron.
authors.affiliation: Dept. Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands. martincmichel@yahoo.de
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
authors.forename: Peter
authors.initials: P
authors.lastname: Ochodnicky
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism; D001745:Urinary Bladder Diseases / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists