1. Volume 121, Issue 6, Pages 1473-1484 (December 2001)
Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat 
John Lee, Francesco Azzaroli, Lin Wang, Carol J. Soroka, Alessandro Gigliozzi, Kenneth D.R. Setchell, Werner Kramer, James L. Boyer 
Gastroenterology 
Volume 121, Issue 6, Pages (December 2001)
DOI: /gast
Copyright © 2001 American Gastroenterological Association Terms and Conditions

2. Fig. 1
Serum and urine bile salt concentrations during CBDL. Serum bile salts are maximally elevated after 3 days of CBDL. Although the levels begin to fall after 3 days of CBDL, they remain higher than control values for up to 14 days of CBDL. Urine bile salt output is progressively increased throughout the 14 days of CBDL.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

3. Fig. 2
Typical negative ion FAB-MS spectra comparing the urinary bile acid excretion patterns of Wistar and TR− rats with and without CBDL. Urine was collected 7 days after ligation and comparable volumes were taken for analysis. The major bile acid species are indicated by their pseudomolecular ions. Notable was the absence of bile acid sulfates in any of the samples analyzed.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

4. Fig. 3
Alteration in Isbt protein in the liver after 14 days of CBDL as determined by Western blot analysis. (A) A representative blot detecting the monomeric (48 kilodaltons) and dimeric (96 kilodaltons) forms of Isbt in control and 14-day CBDL rats. (B) Densitometry of the 2 bands shows a significant increase of 200% in Isbt protein after 14 days of CBDL. *P < 0.05.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

5. Fig. 4
Isbt mRNA levels in control and 14-day CBDL livers as determined by RPA. (A) A representative RPA determining Isbt mRNA levels from livers of 3 control and 3 14-day CBDL rats. Cyclophilin was used to normalize the loading. (B) Densitometry of RPA from 4 control and 4 14-day CBDL rats shows a 300% increase in Isbt mRNA levels in livers of treated animals. *P < 0.05.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

6. Fig. 5
Changes in the Isbt protein and mRNA levels in control and 14-day CBDL rat kidneys. (A) A representative Western blot demonstrating a decrease in the 96-kilodalton band in kidneys from 14-day CBDL rats. Lane 1 represents ileal membrane as a positive control. (B) A representative RPA showing a decrease in Isbt mRNA in kidneys from 14-day CBDL rats. (C) Densitometry of Western blots and RPA from kidneys of 4 animals in each group shows a significant decrease in both Isbt protein and mRNA after 14 days of CBDL. *P < 0.005, +P <
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

7. Fig. 6
Mrp2 protein and mRNA levels in kidneys after 14 days of CBDL. (A) Western blot demonstrates an increase in Mrp2 protein in kidneys in 14-day CBDL rats compared with controls. (B) A representative RPA showing levels of Mrp2 mRNA in control and 14-day CBDL rat kidneys. (C) Densitometry of Western blots and RPA from kidneys of 3 animals in each group shows a significant increase in Mrp2 protein (*P < 0.05) but no significant change in Mrp2 mRNA levels.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

8. Fig. 7
Immunofluorescent detection of Isbt and Mrp2 in control and 14-day CBDL rat kidneys. (A and B) Isbt is expressed on the apical membrane of proximal tubules in control animals and staining is decreased after 14 days of CBDL. (C and D) Although Mrp2 is also expressed on the apical membrane of proximal tubules in control animals, staining is increased after 14 days of CBDL. Bar = 25 μm.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

9. Fig. 8
Immunofluorescent detection of Isbt in control and 14-day CBDL rat livers. (A) Localization of Isbt in the rat liver is restricted to the cholangiocyte (arrowhead). (B) The intensity of staining is decreased in proliferated cholangiocytes after 14 days of CBDL (arrowhead). Bar = 25 μm.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

10. Fig. 9
Expression and functionality of Isbt from BBMVs of sham and BDL rats. (A) A representative Western blot analysis of BBMVs (50 μg of protein) isolated from sham and BDL rats. The position of 2 forms of Isbt are indicated. Three blots were performed, with a mean of 60% decrease seen in the top band. (B) Total and S0960 inhibited taurocholate uptake in BBMVs is compared from sham and CBDL rats. Taurocholate uptake was measured as described in Materials and Methods using BBMVs isolated from sham and BDL rats. Isbt-specific taurocholate uptake values were determined from the difference in the presence and absence of the inhibitor S0960. The figure illustrates the means ± SE of 8 determinations in a representative experiment.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

11. Fig. 10
depicting adaptive changes in the molecular expression of bile salt transporters in hepatocytes, cholangiocytes, kidney, and ileum in response to CBDL in the rat. Ntcp, sodium taurocholate cotransporting polypeptide; Bsep, bile salt export pump; Mrp, multidrug resistance associated protein; t-Asbt, truncated apical sodium dependent bile salt transporter; Isbt, ileal sodium-dependent bile salt transporter; BS, bile salts; and A−, organic anions.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions