Model bile and bile salts accelerate mucin secretion by cultured dog gallbladder epithelial cells.
OBJECTIVE
Hypersecretion of gallbladder mucin has been proposed as a pathogenic factor in gallstone formation. We investigated whether mucin secretion is modulated by biliary constituents using normal, well-differentiated dog gallbladder epithelial cells.


METHODS
Model biles or bile salts were applied to monolayers of epithelial cells. Mucin secretion was studied by measuring the secretion of [3H]N-acetyl-D-glucosamine-labeled glycoproteins.


RESULTS
Model biles with different cholesterol saturation indices increased mucin secretion by the cells to an average 251% after 5 hours of incubation (P < 0.01). Mucin secretion remained elevated during a 24-hour period, suggesting a sustained effect on mucin secretion. There was no relation between the cholesterol or phospholipid concentration and the extent of stimulation of mucin secretion. Taurocholate caused a dose-dependent increase in mucin secretion, suggesting that bile salt was the bile component responsible for the stimulatory effect. At a concentration of 0.5 mmol/L, only the more hydrophobic bile salts taurochenodeoxycholate and taurodeoxycholate, but not the hydrophylic bile salts taurocholate and tauroursodeoxycholate, stimulated mucin secretion (P < 0.01).


CONCLUSIONS
Bile salts play an important role in the regulation of mucin secretion. A shift in the bile salt composition of bile towards the more hydrophobic bile salts may cause mucin hypersecretion, thereby initiating cholesterol gallstone formation.
Klinkspoor
J H
JH
Department of Gastroenterology, University of Amsterdam, Academic Medical Center, The Netherlands.
Kuver
R
R
Savard
C E
CE
Oda
D
D
Azzouz
H
H
Tytgat
G N
GN
Groen
A K
AK
Lee
S P
SP
D000818:Animals; D001646:Bile / Q000378:metabolism / Q000502:physiology*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D013657:Taurodeoxycholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D009077:Mucins; D010743:Phospholipids; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; D013656:Taurocholic Acid; D002784:Cholesterol; D000242:Cyclic AMP