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

W. C. Duane, D. M. Wiegand

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55 Scopus citations

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 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 μeq/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 μeq/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 threefold 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.

Original languageEnglish (US)
Pages (from-to)1044-1049
Number of pages6
JournalJournal of Clinical Investigation
Volume66
Issue number5
DOIs
StatePublished - 1980

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