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

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