Biochemical and Biophysical Research Communications
Sinusoidal efflux of taurocholate correlates with the hepatic expression level of Mrp3
Section snippets
Materials and methods
Materials. Unlabeled and []-labeled TCs (2.0 μCi/nmol) were purchased from Sigma Chemical (St. Louis, MO) and New England Nuclear (Boston, MA), respectively. []-Labeled inulin (2.64 mCi/g) was purchased from New England Nuclear. PB was purchased from Sigma Chemical. Other chemicals used were commercially available and reagent grade products. Male SD rats and EHBRs (7–8 weeks old) were purchased from Nihon SLC (Shizuoka, Japan). Rats were kept in an SPF room until they were 11 weeks old and
Disposition of []TC in the perfused liver of PB-treated SD rats and control SD rats
Previously, we compared the hepatic disposition of []TC in SD rats and EHBRs [37]. In the present study, the isolated livers from control and PB-treated SD rats were additionally perfused with the Krebs–Ringer bicarbonate buffer containing 0.1 μM []TC. The time-profiles for excretion into bile and outflow are shown in Figs. 1A and B, respectively. At 40 min, the value of Vbile/I in high dose PB-treated rats (0.77 ± 0.04) was significantly (P<.05) lower than that in low dose PB-treated (0.89 ±
Discussion
We have previously demonstrated that the PSeff of []TC from hepatocytes to blood is enhanced in EHBRs whose Mrp3 expression level is induced [37], and suggested that Mrp3 may participate in the sinusoidal efflux of []TC. To confirm this hypothesis, in the present study, the PSeff values were also compared in control and PB-treated rats, whose expression level of Mrp3 was enhanced. Kinetic analysis of the washout experiments showed that the PSnet,eff in high dose PB-treated rats was three
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Research on Priority Areas on ABC Proteins 10044243 and on Priority Areas on Epithelial Vectorial Transport 12144201 from the Ministry of Education, Science, and Culture of Japan.
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