Fernandes Vítor S, Hernández Medardo
Department of Physiology, Faculty of Pharmacy, Complutense University of Madrid, 28040, Madrid, Spain.
Basic Clin Pharmacol Toxicol. 2016 Oct;119 Suppl 3:34-41. doi: 10.1111/bcpt.12565. Epub 2016 Mar 18.
This MiniReview focuses on the role played by nitric oxide (NO) and hydrogen sulfide (H S) in physiology of the upper and lower urinary tract. NO and H S, together with carbon monoxide, belong to the group of gaseous autocrine/paracrine messengers or gasotransmitters, which are employed for intra- and intercellular communication in almost all organ systems. Because they are lipid-soluble gases, gaseous transmitters are not constrained by cellular membranes, so that their storage in vesicles for later release is not possible. Gasotransmitter signals are terminated by falling concentrations upon reduction in production that are caused by reacting with cellular components (essentially reactive oxygen species and NO), binding to cellular components or diffusing away. NO and, more recently, H S have been identified as key mediators in neurotransmission of the urinary tract, involved in the regulation of ureteral smooth muscle activity and urinary flow ureteral resistance, as well as by playing a crucial role in the smooth muscle relaxation of bladder outlet region. Urinary bladder function is also dependent on integration of inhibitory mediators, such as NO, released from the urothelium. In the bladder base and distal ureter, the co-localization of neuronal NO synthase with substance P and calcitonin gene-related peptide in sensory nerves as well as the existence of a high nicotinamide adenine dinucleotide phosphate-diaphorase activity in dorsal root ganglion neurons also suggests the involvement of NO as a sensory neurotransmitter.
本综述聚焦于一氧化氮(NO)和硫化氢(H₂S)在上下尿路生理过程中所起的作用。NO和H₂S与一氧化碳同属气态自分泌/旁分泌信使或气体递质,几乎在所有器官系统中用于细胞内和细胞间通讯。由于它们是脂溶性气体,气体递质不受细胞膜限制,因此无法储存在囊泡中以供后续释放。气体递质信号通过与细胞成分(主要是活性氧和NO)反应、与细胞成分结合或扩散而导致产生减少,浓度下降从而终止。NO以及最近发现的H₂S已被确定为尿路神经传递中的关键介质,参与输尿管平滑肌活动、尿流输尿管阻力的调节,并且在膀胱出口区域的平滑肌松弛中起关键作用。膀胱功能还依赖于从尿路上皮释放的抑制性介质(如NO)的整合。在膀胱底部和远端输尿管,感觉神经中神经元型一氧化氮合酶与P物质和降钙素基因相关肽的共定位以及背根神经节神经元中高烟酰胺腺嘌呤二核苷酸磷酸黄递酶活性的存在也表明NO作为感觉神经递质参与其中。