Abstract

The mechanism by which the stomach protects itself from autodigestion by the acid contained within its lumen has not been elucidated to date. In this proposal we outline a series of experiments to investigate the role of intrinsic and extrinsic surface-active phospholipids in this protective mechanism. These studies developed from preliminary findings from our laboratory which indicated that: 1) amphoteric phospholipids present in pulmonary surfactant have the capability of increasing the hydrophobic (non-wettable) property of inert and biological surfaces; 2) these same surface-active molecules are present in the gastric juice and mucosal lining; 3) the intact gastric mucosal lining is highly hydrophobic whereas it is rapidly converted to a wettable surface after the stomach is exposed to the barrier breakers, aspirin and bile acid; and 4) acid-induced ulcerogensis and bleeding are markedly reduced if rats are pretreated with an liposomal suspension of extrinsic surface-active phospholipids. It is our contention that these surface-active phospholipids are adsorbed onto the surface of the gastric mucosal surface and in doing so form and non-wettable hydrophobic layer between the acidic luminal contents and the gastric epithelium. In the proposed studies we plan to test this hypothesis by investigating: 1) the relationship between surface hydrophobicity and the integrity of the """"""""Gastric Mucosal Barrier""""""""; 2) the localization of the intrinsic surface-active phospholipids within the gastric mucosa and their cell of origin; 3) the ability of extrinsic phospholipids to protect against contrasting forms of experimentally-induced gastric and duodenal ulcer and 4) the possible mediator role of intrinsic surface-active phospholipids in prostagladin-induced cytoprotection. The latter possibility seems particularly appealing since we have obtained preliminary evidence that prostaglandins acutely stimulate the concentration of surface-active phospholipids within the rodent gastric mucosa.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033239-03
Application #
3231628
Study Section
(GCN)
Project Start
1983-12-01
Project End
1987-03-31
Budget Start
1985-12-01
Budget End
1987-03-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Texas Health Science Center Houston
Department
Type
Overall Medical
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225

  Publications

Shao, J; Sartor, R B; Dial, E et al. (2000) Expression of intrinsic factor in rat and murine gastric mucosal cell lineages is modified by inflammation. Am J Pathol 157:1197-205
Lichtenberger, L M; Dial, E J; Ottlecz, A et al. (1999) Attenuation of hydrophobic phospholipid barrier is an early event in Helicobacter felis-induced gastritis in mice. Dig Dis Sci 44:108-15
Serna, J H; Genta, R M; Lichtenberger, L M et al. (1997) Invasive Helicobacter-like organisms in feline gastric mucosa. Helicobacter 2:40-3
Lichtenberger, L M; Ulloa, C; Romero, J J et al. (1996) Nonsteroidal anti-inflammatory drug and phospholipid prodrugs: combination therapy with antisecretory agents in rats. Gastroenterology 111:990-5
Lichtenberger, L M; Ulloa, C; Vanous, A L et al. (1996) Zwitterionic phospholipids enhance aspirin's therapeutic activity, as demonstrated in rodent model systems. J Pharmacol Exp Ther 277:1221-7
Goddard, P J; Lichtenberger, L M (1995) In vitro recovery of canine gastric mucosal surface hydrophobicity and potential difference after aspirin damage. Dig Dis Sci 40:1357-9
Lichtenberger, L M; Wang, Z M; Romero, J J et al. (1995) Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospholipids: insight into the mechanism and reversal of NSAID-induced gastrointestinal injury. Nat Med 1:154-8
Go, M F; Chan, K Y; Versalovic, J et al. (1995) Cluster analysis of Helicobacter pylori genomic DNA fingerprints suggests gastroduodenal disease-specific associations. Scand J Gastroenterol 30:640-6
Lichtenberger, L M; Romero, J J (1994) Effect of ammonium ion on the hydrophobic and barrier properties of the gastric mucus gel layer: implications on the role of ammonium in H. pylori-induced gastritis. J Gastroenterol Hepatol 9 Suppl 1:S13-9
Kao, Y C; Lichtenberger, L M (1993) Effect of 16,16-dimethyl prostaglandin E2 on lipidic organelles of rat gastric surface mucous cells. Gastroenterology 104:103-13

Showing the most recent 10 out of 21 publications