title: Expression and electrophysiological characteristics of P2X3 receptors in interstitial cells of Cajal in rats with partial bladder outlet obstruction.
abstract: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: In the urinary bladder, histological studies suggest a network of functionally connected interstitial cells of Cajal (ICCs) are located between the urothelium and sensory nerve endings, which might transfer signals directly between them. Purinergic P2X3 receptors may play roles in the micturition reflex pathway, and its expression profiles in ICCs could be altered in urinary bladder dysfunction. The present experiments showed a novel time-dependent P2X3 receptor up-regulation in ICCs in an experimental rat model of partial bladder outlet obstruction.
  
  
  OBJECTIVE
  To investigate the expression and electrophysiological characteristics of purinergic P2X3 receptors in interstitial cells of Cajal (ICCs) at different time points after partial bladder outlet obstruction (PBOO) in rats.
  
  
  METHODS
  In all, 48 female Sprague-Dawley rats were randomly divided into four groups: 4, 6 and 8 week PBOO groups and sham-operated controls. At 4 weeks after surgery, cystometry was performed to investigate bladder function in vivo. Subsequently, the rats were humanely killed at 4, 6 or 8 weeks and the bladders were harvested for measurements. P2X3 expression in ICCs of bladder was investigated by immunofluorescent staining. The level of P2X3 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Inward currents in corresponding ICCs after PBOO were investigated electrophysiologically.
  
  
  RESULTS
  Cystometrography showed a valid increase in maximum detrusor pressure in rats subjected to PBOO. The bladder weight in the PBOO group was significantly higher than that in the control group. In contrast to sham rats, there was a significant increase in the intensity of P2X3 staining in the ICCs in all PBOO groups. C-kit labelled isolated ICCs were strongly stained with the P2X3 antibody. RT-PCR showed that the expression of P2X3 mRNA was significantly up-regulated at 4, 6 and 8 weeks in the ICCs from the PBOO rats. In the ICCs, the mean peak amplitude of inward currents was significantly increased in the PBOO groups compared with the control group.
  
  
  CONCLUSIONS
  The expression of P2X3 receptors showed a time dependent up-regulation in the ICCs of the bladder in rats with PBOO. PBOO induced the potentiation of P2X3 receptors function, as evidenced by α, β-methylene ATP-enhanced inward currents in the ICCs of the rat bladder.
authors.affiliation: Department of Urology, Xijing Hospital, Xi'an, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Xue
authors.forename: Qing
authors.initials: Q
authors.lastname: Miao
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Mao
authors.forename: Liping
authors.initials: L
authors.lastname: Yao
authors.forename: Jianlin
authors.initials: J
authors.lastname: Yuan
authors.forename: Weijun
authors.initials: W
authors.lastname: Qin
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hang
authors.initials: H
authors.lastname: Sun
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: He
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002450:Cell Communication; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D005260:Female; D056885:Interstitial Cells of Cajal / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058477:Receptors, Purinergic P2X3 / Q000096:biosynthesis*; D015854:Up-Regulation; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D058477:Receptors, Purinergic P2X3