Rat organic anion transporter 2 (rOat2) is abundantly expressed in the live
r and localized to the basolateral membrane. A previous study using the Xen
opus laevis oocyte expression system has shown that rOat2 transports organi
c anions such as salicylate (Sekine et al., 1998) and, in the present study
, rOat2 was characterized using a mammalian expression system. In addition
to the substrates previously shown to be transported by rOat2, three substr
ates, indomethacin [IDM, Michaelis-Menten constant (K-m) of 0.37 muM] and n
ucleoside derivatives such as 3'-azido-3'-deoxythymidine (AZT, K-m of 26 mu
M) and 2',3'-dideoxycytidine (ddC, K-m of 3.08 mM), were also identified fo
r the first time The rank order of rOat2-mediated transport of these substr
ates was IDM > salicylate > prostaglandin E-2 > AZT > ddC > p-aminohippurat
e (PAH). Ketoprofen, indocyanine green and glibenclamide are potent inhibit
ors of the uptake of [C-14]salicylate via rOat2 (K-i of similar to 12 muM),
while diclofenac, benzoate, verapamil, ibuprofen, and tolbutamide are mode
rate inhibitors (K-i of similar to 150 muM). The affinity of PAH, a common
substrate for the OAT family, for rOat2 is low (K-i > 1 mM) compared with t
he other members of the OAT family (rOat1 and rOat3). Salicylate and IDM ar
e also substrates for rOat1, but their affinity for rOat2 was higher than t
hat for rOatl. The present study shows that rOat2 is a multispecific transp
orter and suggests that it may be involved at least partly, in the hepatic
uptake of IDM, salicyiate and nucleoside derivatives.