title: Mechanism by which bile salt disrupts the gastric mucosal barrier in the dog.
abstract: Bile salts disrupt a functional "gastric mucosal barrier" increasing net forward-diffusion (+) of Na+ and back-diffusion (-) of H+. Studying canine Heidenhain pouches, we attempted to distinguish between two possible mechanisms for this effect: (a) mucosal uptake of bile salt with subsequent cellular injury or (b) dissolution of mucosal lipids by intralumenal bile salt. A 10 mM mixture of six conjugated bile salts simulating the proportions found in human bile induced net Na+ flux of 15.5 +/- 3.2 and net H+ flux of -9.9 +/- 3.3 mueq/min. This change was accompanied by an increase in phospholipid efflux out of gastric mucosa from a base-line value of 13.2 +/- 2.7 to 54.8 +/- 2.8 nmol/min (P < 0.001) and an increase in cholesterol efflux from 11.7 +/- 3.8 to 36.3 +/- 3.2 nmol/min (P < 0.001). Saturation with lecithin (25 mM) and cholesterol (50 mM) blocked disruption of the gastric mucosal barrier by bile salt (Na+ flux - 1.2 +/- 0.9, H+ flux 0.6 +/- 1.8 mueq/min). A 10 mM solution of taurodehydrocholate, a bile salt that does not form micelles, induced no net Na+ (-0.3 +/- 0.8) or H+ flux (-0.7 +/- 1.4) and did not increase efflux of phospholipid (11.3 +/- 1.7) or cholesterol (10.4 +/- 2.0) over base line. Bile salt was absorbed from the mixture of six conjugates at 752 +/- 85 nmol/min. Addition of subsaturation amounts of lecithin (4 mM) reduced bile salt absorption three fold to 252 +/- 57 (P < 0.001), but abnormal Na+ flux (14.1 +/- 3.4) and H+ flux (-15.6 +/- 3.5) persisted. Taurodehydrocholate was absorbed to an intermediate extent (467 +/- 116). Dissolution of mucosal lipids is apparently the mechanism by which bile salt disrupts the gastric mucosal barrier, and presumably at least one mechanism by which bile salt can injure the gastric mucosa.
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D004058:Diffusion; D004285:Dogs; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D010743:Phospholipids; D006859:Hydrogen; D002784:Cholesterol; D012964:Sodium