Adaptive regulation of the ileal apical sodium dependent bile acid transporter (ASBT) in patients with obstructive cholestasis

Petr Hruz ¹, Christian Zimmermann ¹, Heike Gutmann ¹, Lukas Degen ², Ulrich Beuers ³, Luigi Terracciano ⁴, Juergen Drewe ¹ and Christoph Beglinger ^2*

¹ Div. of Clinical Pharmacology & Toxicology, University Clinic Basel, Switzerland
² Div. of Gastroenterology, University Clinic Basel, Switzerland
³ Ludwig-Maximilians-University, Grosshadern, Munich, Germany
⁴ Department of Pathology, University Clinic Basel, Switzerland

^* To whom correspondence should be addressed. E-mail: beglinger{at}tmr.ch.

Accepted 17 August 2005

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 an adaptive regulation of the human intestinal ASBT exists during obstructive cholestasis is not known.

Methods: Human ASBT mRNA expression along the intestinal tract was analyzed by real time PCR in biopsies of 14 control subjects undergoing both gastroscopy and colonoscopy. Their duodenal ASBT mRNA expression was compared to 20 patients with obstructive cholestasis. Additionally, in 4 patients with obstructive cholestasis, duodenal ASBT mRNA expression was measured after reconstitution of bile flow.

Results: Normalized ASBT expression in control subjects was highest (mean arbitrary units± SEM) in the terminal ileum 1010 ± 330. Low ASBT expression was found in the colonic segments (8.3±5, 4.9±0.9, 4.8±1.7 and 1.1±0.2, ascending, transverse, descending, and sigmoid colon, respectively). Duodenal ASBT expression of control subjects was found with 171.8±20.3 at about four fold higher levels when compared to 37.9±6.5 (p<0.0001) in patients with obstructive cholestasis. Individual ASBT mRNA expression was inversely correlated with bile acid and bilirubin plasma concentrations. In 4 cholestatic patients average ASBT mRNA increased from 76±18 before to 113±18 after relief of cholestasis (NS). Immunohistochemical assessment indicates that ASBT protein is expressed on the apical surface of the duodenal epithelial cells.

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

Keywords: ASBT, bile acids, cholestasis, transporter

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Dawson, P. A., Lan, T., Rao, A. (2009). Bile acid transporters. J. Lipid Res. 50: 2340-2357 [Abstract] [Full Text]  
• Meier, Y., Eloranta, J. J., Darimont, J., Ismair, M. G., Hiller, C., Fried, M., Kullak-Ublick, G. A., Vavricka, S. R. (2007). Regional Distribution of Solute Carrier mRNA Expression Along the Human Intestinal Tract. Drug Metab. Dispos. 35: 590-594 [Abstract] [Full Text]