Franken J, Uvin P, De Ridder D, Voets T
Br J Pharmacol. 2014 May;171(10):2537-51. doi: 10.1111/bph.12502.
Lower urinary tract dysfunction (LUTd) represents a major healthcare problem. Although it is mostly not lethal, associated social disturbance, medical costs, loss of productivity and especially diminished quality of life should not be underestimated. Although more than 15% of people suffer from a form of LUTd to some extent, pathophysiology often remains obscure. In the past 20 years, transient receptor potential (TRP) channels have become increasingly important in this field of research. These intriguing ion channels are believed to be the main molecular sensors that generate bladder sensation. Therefore, they are intensely pursued as new drug targets for both curative and symptomatic treatment of different forms of LUTd. TRPV1 was the first of its class to be investigated. Actually, even before this channel was cloned, it had already been targeted in the bladder, with clinical trials of intravesical capsaicin instillations. Several other polymodally gated TRP channels, particularly TRPM8, TRPA1 and TRPV4, also appear to play a prominent role in bladder (patho)physiology. With this review, we provide a brief overview of current knowledge on the role of these TRP channels in LUTd and their potential as molecular targets for treatment.
下尿路功能障碍(LUTd)是一个重大的医疗保健问题。尽管它大多不会致命,但相关的社会干扰、医疗成本、生产力损失,尤其是生活质量的下降都不应被低估。虽然超过15%的人在某种程度上患有某种形式的LUTd,但其病理生理学往往仍不清楚。在过去20年里,瞬时受体电位(TRP)通道在该研究领域变得越来越重要。这些引人入胜的离子通道被认为是产生膀胱感觉的主要分子传感器。因此,它们作为治疗不同形式LUTd的根治性和对症治疗的新药靶点而受到密切关注。TRPV1是该类通道中第一个被研究的。实际上,甚至在这个通道被克隆之前,它就已经在膀胱中成为靶点,进行了膀胱内注入辣椒素的临床试验。其他几种多模态门控TRP通道,特别是TRPM8、TRPA1和TRPV4,似乎在膀胱(病理)生理学中也发挥着重要作用。通过这篇综述,我们简要概述了目前关于这些TRP通道在LUTd中的作用及其作为治疗分子靶点的潜力的知识。