title: Comparison of urinary excretion of phenolsulfonphthalein in an animal model for Wilson's disease (Long-Evans Cinnamon rats) with that in normal Wistar rats: involvement of primary active organic anion transporter.
abstract: OBJECTIVE
  The aim of this study was to determine the cause of the decline in phenolsulfonphthalein (PSP) excretion in Long-Evans Cinnamon (LEC) rats.
  
  
  METHODS
  The uptake of PSP into rat renal basolateral membrane vesicles (BLMV) was studied. Cyclosporin A (CYA) was used to modulate an ATP-dependent primary active transporter. PSP was intravenously injected into rats with or without CYA. The transcellular transport of PSP was examined by using primary cultured renal proximal tubule cells (PTC).
  
  
  RESULTS
  No significant difference was found between the uptake of PSP into renal BLMV of Wistar rats and that into renal BLMV of LEC rats. In the presence of CYA, the urinary excretion and the plasma concentrations of PSP in Wistar rats were decreased and increased, respectively. In primary cultured renal PTC from Wistar rats, the basal-to-apical transport of PSP was greater than that in the opposite direction and the basal-to-apical transport of PSP was substantially reduced by the addition of CYA. However, CYA did not affect the basal-to-apical transport of PSP in PTC from LEC rats.
  
  
  CONCLUSIONS
  The results suggest that PSP is transported by primary active organic anion transporter and that the activity level of this transporter is reduced in LEC rats.
authors.affiliation: Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Japan.
authors.forename: Shirou
authors.initials: S
authors.lastname: Itagaki
authors.forename: Soji
authors.initials: S
authors.lastname: Shimamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirano
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sugawara
authors.forename: Sachiho
authors.initials: S
authors.lastname: Nishimura
authors.forename: Michio
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D006527:Hepatolenticular Degeneration / Q000378:metabolism* / Q000652:urine; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D029365:Organic Anion Transporters, ATP-Dependent / Q000037:antagonists & inhibitors / Q000502:physiology*; D010637:Phenolsulfonphthalein / Q000378:metabolism; D051381:Rats; D020332:Rats, Inbred LEC / Q000378:metabolism*; D017208:Rats, Wistar
chemical_list: D029365:Organic Anion Transporters, ATP-Dependent; D016572:Cyclosporine; D010637:Phenolsulfonphthalein