title: Major role of organic anion transporters in the uptake of phenolsulfonphthalein in the kidney.
abstract: Phenolsulfonphthalein is used for testing renal function. However, its excretion mechanism has not been elucidated. The purpose of this study was therefore to elucidate the transporter-mediated excretion system for phenolsulfonphthalein. p-Aminohippuric acid, a substrate of rat organic anion transporter1 (rOat1), and cimetidine, a substrate of rOat3, reduced the urinary excretion of phenolsulfonphthalein. The uptake of phenolsulfonphthalein by kidney slices was found to consist of two components. The IC50 values of rOat1 substrates were higher than those of rOat3 substrates. In the presence of cimetidine, the Eadie-Hofstee plot gave a single straight line. The profile of the phenolsulfonphthalein uptake component in the presence of cimetidine was similar to that of the low-affinity component in the absence of cimetidine. We conclude that rOat1 and rOat3 are involved in the renal uptake of phenolsulfonphthalein and that phenolsulfonphthalein is a high-affinity substrate for rOat3 but is a relatively low-affinity substrate for rOat1.
authors.affiliation: Department of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Shirou
authors.initials: S
authors.lastname: Itagaki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sugawara
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Sachiho
authors.initials: S
authors.lastname: Nishimura
authors.forename: Michio
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Katsumi
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism*; D008297:Male; D027362:Organic Anion Transport Protein 1 / Q000502:physiology*; D027361:Organic Anion Transporters / Q000502:physiology; D029362:Organic Anion Transporters, Sodium-Independent / Q000502:physiology*; D010637:Phenolsulfonphthalein / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D010637:Phenolsulfonphthalein