The physico-chemical basis of the barrier properties of the stomach has yet to be defined. We have reported that the luminal surface of the stomach is uniquely hydrophobic or non- wettable which may prevent luminal (aqueous) ulcerogens from coming in intimate contact with the gastric epithelium. Furthermore, we have demonstrated that certain damaging agents (i.e. aspirin) markedly attenuate this property whereas it is restored by """"""""cytoprotective"""""""" prostaglandins. In the present application we plan to continue these studies and further pursue employing both in vitro (Ussing Chamber) and in vivo studies the effects of a number of clinically relevant barrier breakers (aspirin, bile acids, lysolecithin, ethanol) alone and together with prostaglandin on the surface hydrophobicity of the gastric mucosa. The importance of the restoration of surface hydrophobicity to the stomach's ability to recover from damage will also be investigated. We also plan to continue our studies investigating the role of mucosal surface-active phospholipids (SAPL) in the generation of a protective hydrophobic layer by performing morphological, (SAPL-specific stains and autoradiography and at the light and electron microscopic level), biochemical, biophysical and cell biological studies. Since preliminary morphological data indicates that the mucous cells may be involved in active phospholipid synthesis and secretion, we will attempt to study these processes directly in a monolayer culture of purified gastric mucous cells. The information obtained in the biochemical studies on the SAPL composition of the gastric mucosa will be used to formulate liposomal mixtures whose anti-ulcer activity will be tested in several animal models of experimentally-induced ulcerogenesis. We also plan to characterize the fluidity of the lipids of the gastric mucosal surface using fluorescent polarization spectrometry to access its role in the barrier properties of the stomach.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033239-06
Application #
3231630
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1983-12-01
Project End
1990-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Overall Medical
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
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