Urothelial calcium‐sensing receptor modulates micturition function via mediating detrusor activity and ameliorates bladder hyperactivity in rats

Wei Yi Wu, Shih Pin Lee, Bing Juin Chiang*, Wei Yu Lin, Chiang Ting Chien

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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) ac-tivity, whereas its inhibition via the CaSR antagonist, NPS‐2143 hydrochloride (NPS), increased detrusor activity in in vitro myography experiments. Cystometry, bladder nerve activities record-ing, 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.

Original languageEnglish
Article number960
JournalPharmaceuticals
Volume14
Issue number10
DOIs
Publication statusPublished - 2021 Oct

Keywords

  • Chemosensory
  • Detrusor activity
  • Micturition
  • Urothelium
  • calcium‐sensing receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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