Cellular mechanisms of pacemaking in the upper urinary tract: effects of sensory neuropeptides and prostaglandins

哺乳动物的上尿路(UUT)用于将尿液从肾内的肾盆通过输尿管推到膀胱，在那里储存直到排尿。尿液通过UUT平滑肌壁的自发蠕动收缩进入膀胱，这与前列腺素的局部释放密切相关。大约10%的人在一生中的某个阶段患有肾结石，其中男性患结石的可能性是女性的2-4倍。肾绞痛的疼痛治疗通常包括开出强效止痛药，以及抗痉挛和非类固醇抗炎药。大多数结石如果很小，就会自发排出。较大的结石需要干预措施，如碎石(体外碎石术)，这是一个门诊程序，或物理切除，使用输尿管镜或内窥镜或在全身麻醉下的开放手术；程序通常需要住院2-7天。该项目将为哺乳动物UUT中感觉神经和内源性前列腺素控制运动的机制提供有价值的信息。特别是，这些研究将有助于寻找特定的抗炎药，这些抗炎药将影响UUT运动的特定方面。更清楚地了解UUT节律性的细胞起源将导致更多知情的非手术干预，以鼓励痛苦的结石的通过。这些信息还将有助于其他形式的肾绞痛、输尿管梗阻和尿路感染的治疗。输尿管淤积是一个需要避免的重要条件，如果不进行治疗，永久性肾脏损害通常会在6周内发生。

The mammalian upper urinary tract (UUT) serves to propel urine from the renal pelvis within the kidney through the ureter to the bladder, where it is stored until micturition. This propulsion of urine from the renal pelvis to the bladder occurs by the means of spontaneous peristaltic contractions in the smooth muscle wall of the UUT, intimately dependent on the localized release of prostaglandins. Approximately 10% of the population suffer from renal calculi (kidney stones) at some stage of their lifetime, with men being 2-4 times more likely than women to have calculi. Pain management of renal colic usually involves the prescribing of strong analgesics, and antispasmodic and nonsteroidal anti-inflammatory agents. Most stones are expelled spontaneously if they are small. Larger stones require interventions such as fragmentation (extracorpereal lithotripsy), which is an out patient procedure, or physical removal, using ureterscopes or endoscopes or open surgery under general anesthesia; procedures usually requiring hospital stays of 2-7 days. This project will provide valuable information on the mechanisms by which sensory nerves and endogenous prostaglandins control motility in the mammalian UUT. In particular, these studies will contribute to the search of specific anti-inflammatory agents which will affect particular aspects of UUT motility. A clearer understanding of the cellular origin of UUT rhythmicity will lead to more informed non-surgical interventions to encourage the passing of painful calculi. Such information will also aid in the treatments of other forms of renal colic, during ureteric obstruction, and urinary tract infection. Ureteric stasis is an important condition to avoid, if left untreated permanent kidney damage usually occurs within 6 weeks.