Mechanism by which bile salt disrupts the gastric mucosal barrier in the dog

The Journal of Clinical Investigation
W C Duane, D M Wiegand

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...Continue Reading

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Related Concepts

Bile Salts
Epicholesterol
Diffusion
Canis familiaris
Structure of Pyloric Gland
Hydrogen
Phospholipids
Sodium

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