Abstract：
The transitional epithelial cells (urothelium) that line the lumen of the urinary bladder form a barrier between potentially harmful pathogens, toxins, and other bladder contents and the inner layers of the bladder wall. The urothelium, however, is not simply a passive barrier, as it can produce signaling factors, such as ATP, nitric oxide, prostaglandins, and other prostanoids, that can modulate bladder function. We investigated whether substances produced by the urothelium could directly modulate the contractility of the underlying urinary bladder smooth muscle. Force was measured in isolated strips of mouse urinary bladder with the urothelium intact or denuded. Bladder strips developed spontaneous tone and phasic contractions. In urothelium-intact strips, basal tone, as well as the frequency and amplitude of phasic contractions, were 25%, 32%, and 338% higher than in urothelium-denuded strips, respectively. Basal tone and phasic contractility in urothelium-intact bladder strips were abolished by the cyclooxygenase (COX) inhibitor indomethacin (10 µM) or the voltage-dependent Ca2+ channel blocker diltiazem (50 µM), whereas blocking neuronal sodium channels with tetrodotoxin (1 µM) had no effect. These results suggest that prostanoids produced in the urothelium enhance smooth muscle tone and phasic contractions by activating voltage-dependent Ca2+ channels in the underlying bladder smooth muscle. We went on to demonstrate that blocking COX inhibits the generation of transient pressure events in isolated pressurized bladders and greatly attenuates the afferent nerve activity during bladder filling, suggesting that urothelial prostanoids may also play a role in sensory nerve signaling.NEW & NOTEWORTHY This paper provides evidence for the role of urothelial-derived prostanoids in maintaining tone in the urinary bladder during bladder filling, not only underscoring the role of the urothelium as more than a barrier but also contributing to active regulation of the urinary bladder. Furthermore, cyclooxygenase products greatly augment sensory nerve activity generated by bladder afferents during bladder filling and thus may play a role in perception of bladder fullness.
摘要：
膀胱腔内的过渡上皮细胞（尿路上皮）在潜在有害的病原体之间形成屏障，毒素,和其他膀胱内容物和膀胱壁的内层。尿路上皮,然而,不仅仅是一个被动的障碍，因为它可以产生信号因子，比如ATP,一氧化氮,前列腺素和其他前列腺素，可以调节膀胱功能。我们研究了由尿路上皮产生的某些物质是否可以直接调节潜在的膀胱平滑肌的收缩性。在尿路上皮完整或裸露的小鼠膀胱的分离带中测量力。膀胱条出现自发性张力和阶段性收缩。在尿路上皮完整的条带中，基音,以及阶段性收缩的频率和幅度，25%,32%,比尿路上皮剥脱的条带高338%，分别。环加氧酶（COX）抑制剂吲哚美辛（10mM）或电压依赖性Ca2通道阻滞剂地尔硫卓（50mM）消除了尿路上皮完整的膀胱条的基本张力和阶段性收缩力，而用河豚毒素（1mM）阻断神经元钠通道没有效果。这些结果表明，尿路上皮中产生的前列腺素通过激活下方膀胱平滑肌中的电压依赖性Ca2通道来增强平滑肌张力和阶段性收缩。我们继续证明，阻断COX可抑制孤立的加压膀胱中瞬时压力事件的产生，并大大减弱膀胱充盈期间的传入神经活动，提示尿路上皮类前列腺素也可能在感觉神经信号传导中起作用。
