Elsevier

Journal of Hepatology

Volume 27, Issue 6, December 1997, Pages 1051-1056
Journal of Hepatology

Expression of the liver Na+-independent organic anion transporting polypeptide (oatp-1) in rats with bile duct ligation

https://doi.org/10.1016/S0168-8278(97)80149-3Get rights and content

Abstract

Background/Aims: In rats with cholestasis due to bile duct ligation, the expression of the Na+-dependent taurocholate co-transporting polypeptide, the major uptake system for conjugated bile acids in hepatocytes, is down-regulated. Our purpose was to examine the expression of the organic anion transporting polypeptide, a Na+-independent uptake system for bile acids and organic anions, in rats with bile duct ligation, and to compare the expression of organic anion transporting polypeptide to that of Na+-dependent taurocholate co-transporting polypeptide.

Methods: Rats with bile duct ligation were studied after 1, 3 or 7 days. The expression of organic anion transporting polypeptide and Na+-dependent taurocholate co-transporting polypeptide proteins was examined by Western blot analysis and steady-state mRNA levels were determined by Northern blot analysis using cDNAs encoding organic anion transporting polypeptide and Na+-dependent taurocholate co-transporting polypeptide. Sham-operated animals were used as controls.

Results: The expression of organic anion transporting polypeptide protein was slightly, but not significantly, decreased 1 day after ligation (10.3%); it was markedly decreased after 3 days (56.9%; p<0.03) and 7 days (45.8%; p<0.05) compared to sham-operated animals. Steady-state mRNA levels of organic anion transporting polypeptide was decreased by 79.7% (p<0.04), 48.8% (p<0.02) and 57.4% (p<0.02) after 1, 3 and 7 days respectively. For comparison, Na+-dependent taurocholate co-transporting polypeptide protein and mRNA levels were decreased by 73.8% (p<0.03) and 70.0% (p<0.05) at 1 day and remained low after 3 and 7 days.

Conclusions: In rats with bile duct ligation, the expression of organic anion transporting polypeptide protein and mRNA is down-regulated. Down-regulation of organic anion transporting polypeptide seems less pronounced than that of Na+-dependent taurocholate co-transporting polypeptide. Nevertheless, it could contribute to a decreased uptake of potentially toxic bile acids or organic anions in this situation.

References (27)

Cited by (98)

  • Mechanisms of Hepatocyte Organic Anion Transport

    2018, Physiology of the Gastrointestinal Tract, Sixth Edition
  • Mechanisms of Hepatocyte Organic Anion Transport

    2012, Physiology of the Gastrointestinal Tract, Two Volume Set
  • Mechanisms of Hepatocyte Organic Anion Transport

    2012, Physiology of the Gastrointestinal Tract
  • Regulation of Hepatobiliary Transporters during Liver Injury

    2010, Comprehensive Toxicology, Second Edition
  • Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration

    2007, Biochimica et Biophysica Acta - Molecular Cell Research
    Citation Excerpt :

    As an important protective regulatory step, the basolateral Na+-dependent bile acid uptake system, Ntcp, is downregulated to prevent further bile acid uptake by hepatocytes [191–193]. While Oatp1 (Oatp1a1) is also decreased during obstructive cholestasis, maintained Oatp2 (Oatp1a4) and Oatp4 (Oatp1b2) expression ensures continuos elimination of other organic anions into the bile under these conditions and contributes to the progressive nature of obstructive liver damage [192,194,195]. Most prominent is the downregulation of rat Mrp2 to less than 10% of the normal expression after 7 days of CBDL [40].

  • Liver-homing of purified glucose oxidase: A novel in vivo model of physiological hepatic oxidative stress (H<inf>2</inf>O<inf>2</inf>)

    2007, Journal of Hepatology
    Citation Excerpt :

    Liver samples were homogenized in PBS on ice in the presence of protease inhibitors (Protease inhibitor cocktail P8340; Sigma, Deisenhofen, Germany) using a glass homogenizer (Wheaton, Millville, NJ). Western blotting was performed using the conditions as described previously [26–32] with the antibody dilutions shown in Table 1. Secondary horseradish peroxidase-conjugated goat anti-rabbit, goat anti-guinea pig, and goat anti-mouse IgG were used at dilutions of 1:3000.

View all citing articles on Scopus
View full text