Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats
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...
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MDPI AG
2021-09-01
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| author | Wei-Yi Wu Shih-Pin Lee Bing-Juin Chiang Wei-Yu Lin Chiang-Ting Chien |
| author_facet | Wei-Yi Wu Shih-Pin Lee Bing-Juin Chiang Wei-Yu Lin Chiang-Ting Chien |
| author_sort | Wei-Yi Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T06:17:04Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T06:17:04Z |
| publishDate | 2021-09-01 |
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| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-49535763861845e797d781cdd7a9d0772023-11-22T19:35:06ZengMDPI AGPharmaceuticals1424-82472021-09-01141096010.3390/ph14100960Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in RatsWei-Yi Wu0Shih-Pin Lee1Bing-Juin Chiang2Wei-Yu Lin3Chiang-Ting Chien4Department of Life Science, School of Life Science, College of Science, National Taiwan Normal University, Taipei 11677, TaiwanDepartment of Public Health, International College, Krirk University, Bangkok 10220, ThailandDepartment of Life Science, School of Life Science, College of Science, National Taiwan Normal University, Taipei 11677, TaiwanDepartment of Life Science, School of Life Science, College of Science, National Taiwan Normal University, Taipei 11677, TaiwanDepartment of Life Science, School of Life Science, College of Science, National Taiwan Normal University, Taipei 11677, TaiwanThe 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.https://www.mdpi.com/1424-8247/14/10/960calcium-sensing receptorchemosensorydetrusor activitymicturitionurothelium |
| spellingShingle | Wei-Yi Wu Shih-Pin Lee Bing-Juin Chiang Wei-Yu Lin Chiang-Ting Chien Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats Pharmaceuticals calcium-sensing receptor chemosensory detrusor activity micturition urothelium |
| title | Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats |
| title_full | Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats |
| title_fullStr | Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats |
| title_full_unstemmed | Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats |
| title_short | Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats |
| title_sort | urothelial calcium sensing receptor modulates micturition function via mediating detrusor activity and ameliorates bladder hyperactivity in rats |
| topic | calcium-sensing receptor chemosensory detrusor activity micturition urothelium |
| url | https://www.mdpi.com/1424-8247/14/10/960 |
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