Model bile and bile salts accelerate mucin secretion by cultured dog gallbladder epithelial cells

Gastroenterology. 1995 Jul;109(1):264-74. doi: 10.1016/0016-5085(95)90293-7.

Abstract

Background & aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / metabolism
  • Bile / physiology*
  • Bile Acids and Salts / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cholesterol / metabolism
  • Cyclic AMP / metabolism
  • Dogs
  • Dose-Response Relationship, Drug
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Gallbladder / drug effects
  • Gallbladder / metabolism*
  • Mucins / metabolism*
  • Phospholipids / metabolism
  • Taurochenodeoxycholic Acid / pharmacology
  • Taurocholic Acid / pharmacology
  • Taurodeoxycholic Acid / pharmacology

Substances

  • Bile Acids and Salts
  • Mucins
  • Phospholipids
  • Taurochenodeoxycholic Acid
  • Taurodeoxycholic Acid
  • Taurocholic Acid
  • Cholesterol
  • Cyclic AMP