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.
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.
Itagaki
Shirou
S
Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Japan.
Shimamoto
Soji
S
Hirano
Takeshi
T
Iseki
Ken
K
Sugawara
Mitsuru
M
Nishimura
Sachiho
S
Fujimoto
Michio
M
Kobayashi
Michiya
M
Miyazaki
Katsumi
K
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
D029365:Organic Anion Transporters, ATP-Dependent; D016572:Cyclosporine; D010637:Phenolsulfonphthalein