Taurohyodeoxycholate- and tauroursodeoxycholate-induced hypercholeresis is augmented in bile duct ligated rats.
OBJECTIVE
Taurohyodeoxycholate (THDCA) and tauroursodeoxycholate (TUDCA) induce more bile flow per molecule excreted compared to endogenous bile acids. The aim of this study is to determine if the hypercholeretic effect of tauroursodeoxycholate or taurohyodeoxycholate in normal and bile duct ligated (BDL) rats is due to increased ductal secretion.


METHODS
Normal or BDL rats were infused with tauroursodeoxycholate or taurohyodeoxycholate and bile flow, bicarbonate, bile salt, cholesterol, and phospholipid secretion were measured. Cholangiocytes were stimulated with taurohyodeoxycholate or tauroursodeoxycholate, and secretin-stimulated secretion was measured.


RESULTS
Taurohyodeoxycholate and tauroursodeoxycholate increased bile flow more in BDL than normal rats. Tauroursodeoxycholate increased bicarbonate secretion more in BDL compared to normal rats. Taurohyodeoxycholate when infused with taurocholate increased bile flow (but not phospholipid excretion) to a greater degree in BDL compared to normal rats. Taurohyodeoxycholate and tauroursodeoxycholate decreased secretin-stimulated cholangiocyte secretion.


CONCLUSIONS
Consistent with a ductal origin for bile acid-induced hypercholeresis, taurohyodeoxycholate and tauroursodeoxycholate produced a greater hypercholeresis in BDL than normal rats. Tauroursodeoxycholate- (but not taurohyodeoxycholate-) stimulated hypercholeresis is associated with increased HCO(3)(-) secretion. Tauroursodeoxycholate increases biliary HCO(3)(-) secretion by a mechanism unrelated to secretin-stimulated cholangiocyte secretion. Taurohyodeoxycholate-induced hypercholeresis in BDL rats is unrelated to enhanced phospholipid excretion.
Baiocchi
Leonardo
L
The Texas A&M University System Health Science Center, College of Medicine, Temple, TX 76504, USA.
Alpini
Gianfranco
G
Glaser
Shannon
S
Angelico
Mario
M
Alvaro
Domenico
D
Francis
Heather
H
Marzioni
Marco
M
Phinizy
Jo Lynne
JL
Barbaro
Barbara
B
LeSage
Gene
G
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D001649:Bile Duct Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D001652:Bile Ducts / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology; D008026:Ligation; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012633:Secretin / Q000494:pharmacology; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid / Q000031:analogs & derivatives*
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D001639:Bicarbonates; D001647:Bile Acids and Salts; D010743:Phospholipids; D012633:Secretin; C083510:taurohyodeoxycholic acid; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; C031655:ursodoxicoltaurine; D002784:Cholesterol; C095122:multidrug resistance protein 3