title: Evidence of Nonuniformity in Urothelium Barrier Function between the Upper Urinary Tract and Bladder.
abstract: OBJECTIVE
  We compared the relative permeability of upper urinary tract and bladder urothelium to mitomycin C.
  
  
  METHODS
  Ex vivo porcine bladder, ureters and kidneys were dissected out and filled with 1 mg ml(-1) mitomycin C. At 60 minutes the organs were emptied and excised tissue samples were sectioned parallel to the urothelium. Sectioned tissue was homogenized and extracted mitomycin C was quantified. Transurothelial permeation across the different urothelia was calculated by normalizing the total amount of drug extracted to the surface area of the tissue sample. Average mitomycin C concentrations at different tissue depths (concentration-depth profiles) were calculated by dividing the total amount of drug recovered by the total weight of tissue.
  
  
  RESULTS
  Mitomycin C permeation across the ureteral urothelium was significantly greater than across the bladder and renal pelvis urothelium (9.07 vs 0.94 and 3.61 μg cm(-2), respectively). Concentrations of mitomycin C in the ureter and kidney were markedly higher than those achieved in the bladder at all tissue depths. Average urothelial mitomycin C concentrations were greater than 6.5-fold higher in the ureter and renal pelvis than in the bladder.
  
  
  CONCLUSIONS
  To our knowledge we report for the first time that the upper urinary tract and bladder show differing permeability to a single drug. Ex vivo porcine ureter is significantly more permeable to mitomycin C than bladder urothelium and consequently higher mitomycin C tissue concentrations can be achieved after topical application. Data in this study correlate with the theory that mammalian upper tract urothelium represents a different cell lineage than that of the bladder and it is innately more permeable to mitomycin C.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, Wales, United Kingdom.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Williams
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, Wales, United Kingdom.
authors.forename: Luke
authors.initials: L
authors.lastname: Barnard
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, Wales, United Kingdom. Electronic address: allendercj@cf.ac.uk.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Allender
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, Wales, United Kingdom.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Bowen
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, Wales, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Gumbleton
authors.affiliation: Department of Research and Development, Boston Scientific, Urology and Women's Health Division, Marlborough, Massachusetts.
authors.forename: Tim
authors.initials: T
authors.lastname: Harrah
authors.affiliation: Department of Urology, University Hospital of Wales, Cardiff, Wales, United Kingdom.
authors.forename: Aditya
authors.initials: A
authors.lastname: Raja
authors.affiliation: Department of Urology, University Hospital of Wales, Cardiff, Wales, United Kingdom.
authors.forename: Hrishi B
authors.initials: HB
authors.lastname: Joshi
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D016685:Mitomycin / Q000493:pharmacokinetics*; D010539:Permeability; D013552:Swine; D014513:Ureter / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism*
chemical_list: D016685:Mitomycin
keywords: kidney; mitomycin; ureter; urinary bladder; urothelium