title: The effects of Glivec on the urinary bladder excitation of rats with suprasacral or sacral spinal cord transection.
abstract: BACKGROUND
  To investigate the effects of the c-kit blocker imatinib mesylate (Glivec) on the bladders of animals with suprasacral cord injury (SSCI) and sacral cord injury (SCI).
  
  
  METHODS
  We randomized 60 female Sprague-Dawley rats into control, sham, SSCI (T8/9 transection), and SCI (S1-3 transection) groups. Six weeks later, we evaluated the effects of stepwise Glivec administrations on urinary bladder contraction using cystometry and the detrusor strip stretch-test. We investigated spontaneous calcium transients of kit-positive interstitial cells of Cajal (ICCs) with the preloaded Ca(2+) indicator fluo-3AM. The expression levels of c-kit and the number of ICCs in those bladders were determined using Western blot and fluorescence staining analyses, respectively.
  
  
  RESULTS
  Bladder capacity and compliance were decreased in SSCI bladders and increased in SCI bladders (P<0.05). The amplitude and frequency of spontaneous contractions of detrusor strips, the frequency and relative fluorescence intensity of the spontaneous Ca(2+) waves, and c-kit expression in the bladder were significantly increased in the SSCI group and decreased in the SCI group compared with the control and sham groups (P<0.05). The dose-dependent effects of Glivec also confirmed consistent functional variations in bladder activity.
  
  
  CONCLUSIONS
  The expressions and effects of Glivec were enhanced in SSCI bladders and inhibited in SCI bladders, which may indicate potential roles of ICCs for the c-kit signaling pathway in the pathogenesis of SSCI and SCI bladder.
authors.affiliation: Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Deng
authors.forename: Yongge
authors.initials: Y
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.forename: Longkun
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068877:Imatinib Mesylate; D056885:Interstitial Cells of Cajal / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012447:Sacrum; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D002118:Calcium
keywords: Bladder; Glivec; Interstitial cell; Sacral cord injury; Suprasacral cord injury