TY - JOUR
T1 - Researching Bladder Afferents-Determining the Effects of beta(3)-Adrenergic Receptor Agonists and Botulinum Toxin Type-A
AU - Kanai, Anthony
AU - Wyndaele, Jean Jacques
AU - Andersson, Karl-Erik
AU - Fry, Christopher
AU - Ikeda, Youko
AU - Zabbarova, Irina
AU - De Wachter, Stefan
PY - 2011
Y1 - 2011
N2 - 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, beta(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. Neurourol. Urodynam. 30:684-691, 2011.
AB - 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, beta(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. Neurourol. Urodynam. 30:684-691, 2011.
KW - beta(3)-adrenergic receptor agonists
KW - bladder afferents
KW - botulinum toxin type-A
KW - optical mapping
U2 - 10.1002/nau.21102
DO - 10.1002/nau.21102
M3 - Article
C2 - 21661014
SN - 0733-2467
VL - 30
SP - 684
EP - 691
JO - Neurourology and Urodynamics
JF - Neurourology and Urodynamics
IS - 5
ER -