In this application we propose to continue our investigation of the importance of surface hydrophobicity and surface-active lipids in the gastric mucosal barrier in both in vivo and in vitro systems. We propose to study the effects of aspirin and other NSAIDs on the surface hydrophobicity of strips of canine gastric mucosa mounted in Ussing chambers and how this effect relates to the ability of these agents to inhibit prostaglandin formation and induce cell injury, as assessed both electophysiologically and morphologically. We will also investigate whether one or more of these NSAID-induced alterations in mucosal properties can be reversed by the addition of gastroprotective synthetic lipid formulations or prostaglandins to the in vitro preparation. We also propose to investigate the in vivo injurious effects of NSAIDs on the GI tract in intact rats, and whether the animals can be protected from these agents by the administration of synthetic lipids that will fortify the mucosa's hydrophobic properties. Another major goal of this project is to experimentally investigate whether Helicobacter pylori may induce gastritis by eroding the hydrophobic lining of the upper GI tract. This will be studied both biochemically by characterizing the phospholipase activity of H. pylori lysates and media filtrates, and by employing sensitive biophysical assays to investigate the ability of bacterial lysates and media filtrates to hydrolyze a phospholipid monolayer as determined by surface tension and contact angle analyses. We plan a series of experiments to confirm our studies which indicate that we may have successfully infected uremic rats with H. pylori, and to study the effect of this bacterial infection on gastric hydrophobic ani-barrier properties. We also propose to employ isotopic and fluorescent precursors to characterize the synthesis, storage and release of phospholipids, triglycerides and glycoproteins in a culture preparation of differentiated and purified gastric mucous cells, and determine the effect of prostaglandins and NSAIDs on these properties. Lastly, we will perform fractionation studies to isolate extracellular and intracellular lipidic structures and/or organelles observed ultrastructurally to assess their biochemical, biophysical and gastroprotective properties and how they may contribute to the maintenance of the stomach's hydrophobic properties.
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