Basu Chakrabarty, Michael Winder, Anthony J Kanai, Hikaru Hashitani, Marcus Drake, Paul Abrams, Christopher H Fry
{"title":"正常和病理性膀胱中的一氧化氮信号通路:它们提供了新的药理学途径吗-ICI-RS 2023。","authors":"Basu Chakrabarty, Michael Winder, Anthony J Kanai, Hikaru Hashitani, Marcus Drake, Paul Abrams, Christopher H Fry","doi":"10.1002/nau.25321","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>The nitric oxide (NO•)/soluble guanylate cyclase/cyclic-GMP (cGMP) signaling pathway is ubiquitous and regulates several functions in physiological systems as diverse as the vascular, nervous, and renal systems. However, its roles in determining normal and abnormal lower urinary tract functions are unclear. The aim was to identify potential therapeutic targets associated with this pathway to manage lower urinary tract functional disorders.</p><p><strong>Methods: </strong>This review summarizes a workshop held under the auspices of ICI-RS with a view to address these questions.</p><p><strong>Results: </strong>Four areas were addressed: NO• signaling to regulate neurotransmitter release to detrusor smooth muscle; its potential dual roles in alleviating and exacerbating inflammatory pathways; its ability to act as an antifibrotic mediator; and the control by nitrergic nerves of lower urinary tract vascular dynamics and the contractile performance of muscular regions of the bladder wall. Central to much of the discussion was the role of the NO• receptor, soluble guanylate cyclase (sGC) in regulating the generation of the enzyme product, the second messenger cGMP. The redox state of sGC is crucial in determining its enzymic activity and the role of a class of novel agents, sGC activators, to optimize activity and to potentially alleviate the consequences of lower urinary tract disorders was highlighted. In addition, the consequences of a functional relationship between nitrergic and sympathetic nerves to regulate vascular dynamics was discussed.</p><p><strong>Conclusions: </strong>Several potential NO•-dependent drug targets in the lower urinary tract were identified that provide the basis for future research and translation to clinical trials.</p>","PeriodicalId":19200,"journal":{"name":"Neurourology and Urodynamics","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nitric oxide signaling pathways in the normal and pathological bladder: Do they provide new pharmacological pathways?-ICI-RS 2023.\",\"authors\":\"Basu Chakrabarty, Michael Winder, Anthony J Kanai, Hikaru Hashitani, Marcus Drake, Paul Abrams, Christopher H Fry\",\"doi\":\"10.1002/nau.25321\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>The nitric oxide (NO•)/soluble guanylate cyclase/cyclic-GMP (cGMP) signaling pathway is ubiquitous and regulates several functions in physiological systems as diverse as the vascular, nervous, and renal systems. However, its roles in determining normal and abnormal lower urinary tract functions are unclear. The aim was to identify potential therapeutic targets associated with this pathway to manage lower urinary tract functional disorders.</p><p><strong>Methods: </strong>This review summarizes a workshop held under the auspices of ICI-RS with a view to address these questions.</p><p><strong>Results: </strong>Four areas were addressed: NO• signaling to regulate neurotransmitter release to detrusor smooth muscle; its potential dual roles in alleviating and exacerbating inflammatory pathways; its ability to act as an antifibrotic mediator; and the control by nitrergic nerves of lower urinary tract vascular dynamics and the contractile performance of muscular regions of the bladder wall. Central to much of the discussion was the role of the NO• receptor, soluble guanylate cyclase (sGC) in regulating the generation of the enzyme product, the second messenger cGMP. 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In addition, the consequences of a functional relationship between nitrergic and sympathetic nerves to regulate vascular dynamics was discussed.</p><p><strong>Conclusions: </strong>Several potential NO•-dependent drug targets in the lower urinary tract were identified that provide the basis for future research and translation to clinical trials.</p>\",\"PeriodicalId\":19200,\"journal\":{\"name\":\"Neurourology and Urodynamics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurourology and Urodynamics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/nau.25321\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/10/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurourology and Urodynamics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/nau.25321","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
Nitric oxide signaling pathways in the normal and pathological bladder: Do they provide new pharmacological pathways?-ICI-RS 2023.
Aims: The nitric oxide (NO•)/soluble guanylate cyclase/cyclic-GMP (cGMP) signaling pathway is ubiquitous and regulates several functions in physiological systems as diverse as the vascular, nervous, and renal systems. However, its roles in determining normal and abnormal lower urinary tract functions are unclear. The aim was to identify potential therapeutic targets associated with this pathway to manage lower urinary tract functional disorders.
Methods: This review summarizes a workshop held under the auspices of ICI-RS with a view to address these questions.
Results: Four areas were addressed: NO• signaling to regulate neurotransmitter release to detrusor smooth muscle; its potential dual roles in alleviating and exacerbating inflammatory pathways; its ability to act as an antifibrotic mediator; and the control by nitrergic nerves of lower urinary tract vascular dynamics and the contractile performance of muscular regions of the bladder wall. Central to much of the discussion was the role of the NO• receptor, soluble guanylate cyclase (sGC) in regulating the generation of the enzyme product, the second messenger cGMP. The redox state of sGC is crucial in determining its enzymic activity and the role of a class of novel agents, sGC activators, to optimize activity and to potentially alleviate the consequences of lower urinary tract disorders was highlighted. In addition, the consequences of a functional relationship between nitrergic and sympathetic nerves to regulate vascular dynamics was discussed.
Conclusions: Several potential NO•-dependent drug targets in the lower urinary tract were identified that provide the basis for future research and translation to clinical trials.
期刊介绍:
Neurourology and Urodynamics welcomes original scientific contributions from all parts of the world on topics related to urinary tract function, urinary and fecal continence and pelvic floor function.