Induction of sodium-dependent bile acid transporter messenger RNA, protein, and activity in rat ileum by cholic acid.
OBJECTIVE
The ileal sodium-dependent bile acid transporter reclaims bile acids from the intestinal lumen to preserve their enterohepatic recirculation. The present studies sought to determine the possible role of enteric bile acids in the molecular regulation of the apical bile acid transporter in rat ileal mucosa.


METHODS
Paired rats were fed a control diet or control diet plus cholic acid (1%) or ursodeoxycholic acid (1%) for 10 days. Other paired rats underwent biliary diversion for 72 hours, followed by intraduodenal infusion of taurocholate or fluid/electrolytes. Transporter protein, messenger RNA (mRNA), and activity were determined in the distal 15 cm of ileal mucosa.


RESULTS
Transporter protein and mRNA levels in cholic acid-fed rats increased approximately threefold above levels in paired rats fed the control diet (P < 0.02). Similarly, sodium-dependent [3H]taurocholate uptake into membrane vesicles from cholic acid-fed rats increased twofold above uptake into vesicles from control-fed rats because of a twofold increase 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 transporter is induced at a pretranslational level by free or taurine-conjugated cholic acid within the small intestine.
Stravitz
R T
RT
Department of Internal Medicine, McGuire Veterans Administration Medical Center and Medical College of Virginia, Virginia Commonwealth University, Richmond 23249, USA.
Sanyal
A J
AJ
Pandak
W M
WM
Vlahcevic
Z R
ZR
Beets
J W
JW
Dawson
P A
PA
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology*; D006913:Hydroxysteroid Dehydrogenases; D007082:Ileum / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology*; D013656:Taurocholic Acid / Q000494:pharmacology; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D002352:Carrier Proteins; D019826:Cholic Acid; D002793:Cholic Acids; D006913:Hydroxysteroid Dehydrogenases; D008562:Membrane Glycoproteins; D011493:Protein Kinase C; D012333:RNA, Messenger; D012964:Sodium; D013656:Taurocholic Acid; C037643:bile acid binding proteins; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)