{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:17:21Z","timestamp":1790691441113,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>The transient receptor potential melastin\u20108 (TRPM8) channel is a \u201ccooling\u201d receptor expressed in primary sensory neurons and can be activated by compounds like menthol or icilin. TRPM8 is involved in the regulation of urinary bladder sensory function and contraction, but the role of TRPM8 in the ureter, particularly in the human ureter, is poorly understood. The aim of this study is to examine the effects of TRPM8 activation on human ureter contraction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human ureters were acquired from 20 patients undergoing radical nephrectomy. Contractions of ureter strips were recorded by an isometric transducer in the organ bath. Ureteral TRPM8 expression in the human ureter was examined by immunofluorescence and western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The two TRPM8 agonists menthol and icilin both reduced the frequency of spontaneous, electrical field stimulation, or neurokinin A\u2010evoked ureteral contractions in a dose\u2010dependent manner. The inhibitory effects were decreased by 10\u2010fold in mucosa\u2010denuded strips. The inhibitory effects of TRPM8 agonists were mimicked by calcitonin gene\u2010related peptide (CGRP), and were blocked by KRP2579 (a TRPM8 antagonist), tetrodotoxin (a sodium channel blocker), olcegepant (BIBN, a CGRP receptor antagonist), SQ22536 (an adenylate cyclase antagonist), or H89 (a nonspecific cAMP\u2010dependent protein kinase A inhibitor). TRPM8 was coexpressed with CGRP on the nerves located in the suburothelial and intermuscular regions and was not expressed in the urothelium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The TRPM8 channel expressed on sensory nerve terminals of the human ureter is involved in the inhibitory sensory neurotransmission and modulate ureter contraction via the CGRP\u2013adenylyl cyclase\u2013protein kinase A pathway. TRPM8 may be involved in stone\u2010induced changes in ureter contraction or pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24689","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T20:20:54Z","timestamp":1621542054000},"page":"1450-1459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Activation of TRPM8 channel inhibits contraction of the isolated human ureter"],"prefix":"10.1002","volume":"40","author":[{"given":"Jiaxin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Urology, The Second Hospital, Cheeloo College of Medicine, Shandong University Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, The Second Hospital, Cheeloo College of Medicine, Shandong University Shandong University  Jinan Shandong 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Chemical Biology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1390-2292","authenticated-orcid":false,"given":"Jonathan M.","family":"Beckel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, The Second Hospital, Cheeloo College of Medicine, Shandong University Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7304-611X","authenticated-orcid":false,"given":"Xiulin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, The Second Hospital, Cheeloo College of Medicine, 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