The rat liver organic anion transporting polypeptide (Oatp1) has been extensively characterized mainly in the Xenopus laevis expression system as a polyspecific carrier transporting organic anions (bile salts), neutral compounds, and even organic cations. In this study, we extended this characterization using a mammalian expression system and confirm the basolateral hepatic expression of Oatp1 with a new antibody. Besides sulfobromophthalein [Michaelis-Menten constant (K_m) of ~3 µM], taurocholate (K_m of ~32 µM), and estradiol- 17-glucuronide (K_m of ~4 µM), substrates previously shown to be transported by Oatp1 in transfected HeLa cells, we determined the kinetic parameters for cholate (K_m of ~54 µM), glycocholate (K_m of ~54 µM), estrone-3-sulfate (K_m of ~11 µM), CRC-220 (K_m of ~57 µM), ouabain (K_m of ~3,000 µM), and ochratoxin A (K_m of ~29 µM) in stably transfected Chinese hamster ovary (CHO) cells. In addition, three new substrates, taurochenodeoxycholate (K_m of ~7 µM), tauroursodeoxycholate (K_m of ~13 µM), and dehydroepiandrosterone sulfate (K_m of ~5 µM), were also investigated. The results establish the polyspecific nature of Oatp1 in a mammalian expression system and definitely identify conjugated dihydroxy bile salts and steroid conjugates as high-affinity endogenous substrates of Oatp1.

sodium-independent organic anion transport; multispecificity; Chinese hamster ovary cells

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