Article Text

PDF
Adaptive regulation of the ileal apical sodium dependent bile acid transporter (ASBT) in patients with obstructive cholestasis
  1. P Hruz1,
  2. C Zimmermann2,
  3. H Gutmann2,
  4. L Degen3,
  5. U Beuers4,
  6. L Terracciano5,
  7. J Drewe2,
  8. C Beglinger3
  1. 1Department of Clinical Pharmacology and Toxicology, and Division of Gastroenterology, University Hospital of Basel, Basel, Switzerland
  2. 2Department of Clinical Pharmacology and Toxicology, University Hospital of Basel, Basel, Switzerland
  3. 3Division of Gastroenterology, University Hospital of Basel, Basel, Switzerland
  4. 4Department of Medicine II, Klinikum Grosshadern, Ludwig-Maximilians-University, München, Germany
  5. 5Department of Pathology, University Hospital of Basel, Basel, Switzerland
  1. Correspondence to:
    Professor C Beglinger
    Division of Gastroenterology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; beglinger{at}tmr.ch

Abstract

Background/aims: The apical sodium dependent bile acid transporter ASBT (SLC10A2) contributes substantially to the enterohepatic circulation of bile acids by their reabsorption from the intestine. In the rat, its adaptive regulation was observed in the kidneys, cholangiocytes, and terminal ileum after bile duct ligation. Whether adaptive regulation of the human intestinal ASBT exists during obstructive cholestasis is not known.

Methods: Human ASBT mRNA expression along the intestinal tract was analysed by real time polymerase chain reaction in biopsies of 14 control subjects undergoing both gastroscopy and colonoscopy. Their duodenal ASBT mRNA expression was compared with 20 patients with obstructive cholestasis. Additionally, in four patients with obstructive cholestasis, duodenal ASBT mRNA expression was measured after reconstitution of bile flow.

Results: Normalised ASBT expression in control subjects was highest (mean arbitrary units (SEM)) in the terminal ileum (1010 (330)). Low ASBT expression was found in colonic segments (8.3 (5), 4.9 (0.9), 4.8 (1.7), and 1.1 (0.2) in the ascending, transverse, descending, and sigmoid colon, respectively). Duodenal ASBT expression in control subjects (171.8 (20.3)) was found to be approximately fourfold higher compared with patients with obstructive cholestasis (37.9 (6.5); p<0.0001). Individual ASBT mRNA expression was inversely correlated with bile acid and bilirubin plasma concentrations. In four cholestatic patients, average ASBT mRNA increased from 76 (18) before to 113 (18) after relief of cholestasis (NS). Immunohistochemical assessment indicated that ASBT protein was expressed on the apical surface of duodenal epithelial cells.

Conclusion: Obstructive cholestasis in humans leads to downregulation of ASBT mRNA expression in the distal part of the human duodenum.

  • ASBT, apical sodium dependent bile acid transporter
  • CBDL, common bile duct ligation
  • UDCA, ursodeoxycholic acid
  • 75SeHCAT, 75Se-homocholic acid taurine
  • MRP, multidrug resistance associated protein
  • ERCP, endoscopic retrograde cholangiopancreatography
  • PPARα, peroxisome proliferator activated receptor α
  • cholestasis
  • ASBT
  • transporter
  • bile acids

Statistics from Altmetric.com

Footnotes

  • Published online first 8 September 2005

  • Conflict of interest: None declared.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.