Bile acid and bile salt disrupt gastric mucosal barrier in the dog by different mechanisms.
The present study was undertaken to assess the mechanism by which protonated taurocholic acid disrupts the gastric mucosal barrier. By the criterion of lecithin solubilization, the critical micellar concentration of taurocholic acid (pH 1) was 4.5 mM, as opposed to 3.0 mM for sodium taurocholate (pH 7). In canine Heidenhain pouches, taurocholic acid significantly increased net forward diffusion of Na+ and backdiffusion of H+ at concentrations of 9, 4.5, and 3.5 mM, indicating that micelle formation was not required for disruption of the gastric mucosal barrier by this bile acid. Saturation of the 9 mM taurocholic acid solution with lecithin (and cholesterol) did not prevent disruption of the gastric mucosal barrier. At 9 mM, taurocholic acid was absorbed from the pouches at a mean rate of 1,150 +/- 115 nmol/min in contrast to an absorption rate of 225 +/- 10 nmol/min for sodium taurocholate at the same concentration. These findings indicate that, unlike ionized bile salts, disruption of the gastric mucosal barrier by taurocholic acid is mediated largely by uptake of bile acid by the gastric mucosa rather than dissolution of mucosal membrane lipids.
D000042:Absorption; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D010713:Phosphatidylcholines / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013656:Taurocholic Acid / Q000494:pharmacology*
D010713:Phosphatidylcholines; D013656:Taurocholic Acid; D012964:Sodium; D002118:Calcium