INDUCTION OF SODIUM-DEPENDENT BILE-ACID TRANSPORTER MESSENGER-RNA, PROTEIN, AND ACTIVITY IN RAT ILEUM BY CHOLIC-ACID

Background & Aims: The ileal sodium-dependent bile acid transporter re claims bile acids from the intestinal lumen to preserve their enterohe patic recirculation. The present studies sought to determine the possi ble role of enteric bile acids in the molecular regulation of the apic al bile acid transporter in rat ileal mucosa. Methods: Paired rats wer e fed a control diet or control diet plus cholic acid (1%) or ursodeox ycholic acid (1%) for 10 days. Other paired rats underwent biliary div ersion for 72 hours, followed by intraduodenal infusion of taurocholat e or fluid/electrolytes. Transporter protein, messenger RNA (mRNA), an d activity were determined in the distal 15 cm of ileal mucosa. Result s: Transporter protein and mRNA levels in cholic acid-fed rats increas ed approximately threefold above levels in paired rats fed the control diet (P < 0.02). Similarly, sodium-dependent [H-3]taurocholate uptake into membrane vesicles from cholic acid-fed rats increased twofold ab ove uptake into vesicles from control-fed rats because of a twofold in crease in maximal transport velocity. In biliary-diverted rats (72-96 hours), transporter protein decreased to 57% +/- 5% of paired controls with intact enterohepatic circulation (P < 0.0001). The intraduodenal infusion of taurocholate (24 hours) in biliary-diverted rats resulted in a time-dependent reinduction of transporter protein expression (3. 5-fold). Conclusions: The expression of the ileal apical bile acid tra nsporter is induced at a pretranslational level by free or taurine-con jugated cholic acid within the small intestine.