Ultrastructural changes in gastric epithelium caused by bile salt

We assessed the influence of bile salt in neutral solution on the morphology and function of the Ussing-chambered stomach mucosa. Guinea pig gastric mucosa was exposed to 5, 10, and 20 mM taurocholic acid in balanced salt solution with glucose. Control tissues were exposed to salt solution without taurocholic acid. During exposure to the bile salt, the pH of the bathing solutions was maintained at 7.0-7.4 with 0.1 M sodium hydroxide. Potential difference, short-circuit current, and resistance of the tissues were recorded every 15 min. The morphologic effects of the bile salt were determined with light and electron microscopy. The 10 and 20 mM concentrations caused significant deterioration of the electrophysiologic measurements and major morphologic alteration on both light and electron microscopic evaluations. The 5 mM concentration of taurocholic acid did not affect the electrophysiologic measurements or the light microscopic appearance of the surface cells. Electron microscopy, however, revealed morphologic changes in over 50% of the specimens examined. These findings demonstrate that in vitro, mammalian gastric mucosa shows significant ultrastructural changes when exposed to physiological concentrations of bile salt in a neutral solution. These changes appear to be subtle in that they are evident on transmission electron microscopy even before significant change can be demonstrated by light microscopy or by standard electrophysiologic measurements.