{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:22:58Z","timestamp":1760235778782,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST-106-2320-B-003-002"],"award-info":[{"award-number":["MOST-106-2320-B-003-002"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The urothelium displays mechano- and chemosensory functions via numerous receptors and channels. The calcium-sensing receptor (CaSR) detects extracellular calcium and modulates several physiological functions. Nonetheless, information about the expression and the role of CaSR in lower urinary tract has been absent. We aimed to determine the existence of urothelial CaSR in urinary bladder and its effect on micturition function. We utilized Western blot to confirm the expression of CaSR in bladder and used immunofluorescence to verify the location of the CaSR in the bladder urothelium via colocalization with uroplakin III A. The activation of urothelial CaSR via the CaSR agonist, AC-265347 (AC), decreased urinary bladder smooth muscle (detrusor) activity, whereas its inhibition via the CaSR antagonist, NPS-2143 hydrochloride (NPS), increased detrusor activity in in vitro myography experiments. Cystometry, bladder nerve activities recording, and bladder surface microcirculation detection were conducted to evaluate the effects of the urothelial CaSR via intravesical administrations. Intravesical AC inhibited micturition reflex, bladder afferent and efferent nerve activities, and reversed cystitis-induced bladder hyperactivity. The urothelial CaSR demonstrated a chemosensory function, and modulated micturition reflex via regulating detrusor activity. This study provided further evidence of how the urothelial CaSR mediated micturition and implicated the urothelial CaSR as a potential pharmacotherapeutic target in the intervention of bladder disorders.<\/jats:p>","DOI":"10.3390\/ph14100960","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:30:33Z","timestamp":1632443433000},"page":"960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0539-7388","authenticated-orcid":false,"given":"Wei-Yi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Life Science, School of Life Science, College of Science, National Taiwan Normal University, Taipei 11677, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7852-8006","authenticated-orcid":false,"given":"Shih-Pin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Public Health, International College, Krirk University, Bangkok 10220, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing-Juin","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Life Science, School of Life Science, College of Science, National Taiwan Normal University, Taipei 11677, Taiwan"},{"name":"College of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan"},{"name":"Department of Urology, Cardinal Tien Hospital, New Taipei City 23148, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Life Science, School of Life Science, College of Science, National Taiwan Normal University, Taipei 11677, Taiwan"},{"name":"Department of Urology, Ministry of Health and Welfare, Taipei Hospital, New Taipei City 24213, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7580-7069","authenticated-orcid":false,"given":"Chiang-Ting","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Life Science, School of Life Science, College of Science, National Taiwan Normal University, Taipei 11677, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1152\/physrev.00041.2019","article-title":"The Urothelium: Life in a Liquid Environment","volume":"100","author":"Dalghi","year":"2020","journal-title":"Physiol. 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