title: Researching bladder afferents-determining the effects of β(3) -adrenergic receptor agonists and botulinum toxin type-A.
abstract: A substantial portion of the current research on lower urinary tract dysfunction is focused on afferent mechanisms. The main goals are to define and modulate the signaling pathways by which afferent information is generated, enhanced and conveyed to the central nervous system. Alterations in bladder afferent mechanisms are a potential source of voiding dysfunction and an emerging source for drug targets. Established drug therapies such as muscarinic receptor antagonists, and two emerging therapies, β(3) -adrenergic receptor agonists and botulinum toxin type-A, may act partly through afferent mechanisms. This review focuses on these two new principles and new and established methods for determining their sites of action. It also provides brief information on the innervation of the bladder, afferent receptors and transmitters and how these may communicate with the urothelium, interstitial cells and detrusor smooth muscle to regulate micturition. Peripheral and central mechanisms of afferent sensitization and myogenic mechanisms that lead to detrusor overactivity, overactive bladder symptoms and urgency sensations are also covered. This work is the result from 'Think Tank' presentations, and the lengthy discussions that followed, at the 2010 International Consultation on Incontinence Research Society meeting in Bristol, UK.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. ajk5@pitt.edu
authors.forename: Anthony
authors.initials: A
authors.lastname: Kanai
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Wyndaele
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Christopher
authors.initials: C
authors.lastname: Fry
authors.forename: Youko
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Irina
authors.initials: I
authors.lastname: Zabbarova
authors.forename: Stefan
authors.initials: S
authors.lastname: De Wachter
mesh_terms: D000200:Action Potentials; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000344:Afferent Pathways / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects* / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D019459:Urothelium / Q000187:drug effects / Q000294:innervation
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D022702:Receptors, Adrenergic, beta-3; D019274:Botulinum Toxins, Type A