Fig. 6.

Time-dependent changes in sinusoidal membrane transporter activities. Primary rat hepatocytes were incubated with radiolabeled transporter probe substrates: [³H]E17BG (1 μM), [¹⁴C]PAH (1 μM), and [³H]MPP+ (1 μM), which are transported by Oatps (a), Oat2 (b), and Oct1 (c), respectively. The incubations were performed as described under Materials and Methods in the presence or absence of estrone 3-sulfate (100 μM), probenecid (50 μM), and tetraethylammonium (250 μM), which are known inhibitors for Oatps, Oat2, and Oct1, respectively. In addition, 4°C incubations were evaluated to determine passive diffusion of the substrate. Cells were lysed in lysis buffer and cellular accumulation of the radiolabeled compounds was determined by scintillation counting. Data were normalized relative to the protein values and are expressed as picomoles per milligram per minute. Data represented are the mean values of three separate experiments performed in triplicate. *, p < 0.05; **, p < 0.01; ***, p < 0.001.