Urothelial effects of oral agents for overactive bladder

被引:16
作者
Andersson K.-E. [1 ]
Fullhase C. [1 ]
Soler R. [1 ]
机构
[1] Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, Medical Center Boulevard
关键词
Muscarinic Receptor; Overactive Bladder; Detrusor Overactivity; Oxybutynin; Tolterodine;
D O I
10.1007/s11934-008-0079-z
中图分类号
学科分类号
摘要
The cholinergic system of the bladder includes muscarinic receptors distributed to detrusor myocytes and structures within mucosa including bladder afferent (sensory) nerves. The receptors have been shown to be involved in afferent signaling from the bladder, but it has not been established to what extent effects on this mucosal signaling pathway contribute to the therapeutic efficacy of the clinically used antimuscarinics. Mucosa can be influenced by antimuscarinics via the bloodstream. However, some antimuscarinics and their active metabolites are excreted in urine in amounts that may affect the mucosal muscarinic receptors from the luminal side. This has not yet been demonstrated to imply superior clinical efficacy. Nevertheless, mucosal afferent signaling pathways are therapeutically interesting targets that should be further explored. Copyright © 2008 by Current Medicine Group LLC.
引用
收藏
页码:459 / 464
页数:5
相关论文
共 43 条
[1]
Andersson K.E., Antimuscarinics for treatment of overactive bladder, Lancet Neurol, 3, pp. 46-53, (2004)
[2]
Andersson K.E., Bladder activation: Afferent mechanisms, Urology, 59, pp. 43-50, (2002)
[3]
Birder L.A., de Groat W.C., Mechanisms of disease: Involvement of the urothelium in bladder dysfunction, Nat Clin Pract Urol, 4, pp. 46-54, (2007)
[4]
de Groat W.C., The urothelium in overactive bladder: Passive bystander or active participant?, Urology, 64, pp. 7-11, (2004)
[5]
Lips K.S., Wunsch J., Zarghooni S., Et al., Acetylcholine and molecular components of its synthesis and release machinery in the urothelium, Eur Urol, 51, pp. 1042-1053, (2007)
[6]
Yoshida M., Inadome A., Maeda Y., Et al., Non-neuronal cholinergic system in human bladder urothelium, Urology, 67, pp. 425-430, (2006)
[7]
Hanna-Mitchell A.T., Beckel J.M., Barbadora S., Et al., Non-neuronal acetylcholine and urinary bladder urothelium, Life Sci, 80, pp. 2298-2302, (2007)
[8]
Chess-Williams R., Muscarinic receptors of the urinary bladder: Detrusor, urothelial and prejunctional, Auton Autacoid Pharmacol, 22, pp. 133-145, (2002)
[9]
Mansfield K.J., Liu L., Mitchelson F.J., Et al., Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: Changes in ageing, Br J Pharmacol, 144, pp. 1089-1099, (2005)
[10]
Mukerji G., Yiangou Y., Grogono J., Et al., Localization of M2 and M3 muscarinic receptors in human bladder disorders and their clinical correlations, J Urol, 176, pp. 367-373, (2006)