Project: Research project


Previous studies have indicated that the gastric mucosa normally is
protected from the damaging effects of luminal acid by preventing diffusion
of acid from the lumen into the mucosa and neutralizing or disposing of H+
ions entering the tissue. Impairment of these protective properties,
rather than hypersecretion of acid is generally held to be the cause of
acute mucosal erosions elicited by topical agents of injury or systemic
sepsis or stress. Recent work in isolated gastric epithelial systems,
however, has suggested: 1) that transport and permeability processes
located in the basolateral (i.e. serosal-side) cell membrane regulate
intracellular ion composition and pH; 2) that processes leading to
basolateral uptake of HCO3- or extrusion of H+ may depend substantially on
cotransport or exchange mechanisms with Na+, K+ or C1-; and 3) that topical
agents of injury such as aspirin or bile salts may not only reduce the
resistance of the epithelium to back-diffusion of acid, but they may
directly impair these cellular mechanisms of H+ neutralization or disposal.
To further define these protective mechanisms at the cellular level, the
proposed studies are designed: 1) to identify basolateral mechanisms which
regulate intracellular levels of Na+, K+ and C1-; 2) to examine the
basolateral co-transport mechanisms by which the cell uses these ions to
take up HCO3- or extrude H+ in order to preserve cell pH; 3) to evaluate
the effects of topical agents of injury on the cell's ability to handle
experimental acid loads, independent of their effects on permeability to
luminal acid. These three sets of specific aims will be pursued using
intracellular microelectrode techniques in an in vitro model of surface
epithelium from the gastric antrum of the amphibian, Necturus maculosus. The first set will be addressed by defining the contributions of the
different permeability and transport properties which regulate
intracellular levels of Na+, K+ and C1-. These studies will also examine
the influence of changes in luminal acidity and nutrient composition on the
processes which regulate intracellular levels of these ions. The second
set of studies will be directed at identifying specific processes such as
Na+/H+ or C1-/HCO3- exchange in the cell's ability to buffer an acid load
and evaluating the dependence of these processes on intracellular ion
composition. Further studies will evaluate the influence of cellular
regulatory agents such as prostaglandin or cAMP on the cell's ability to
maintain ion composition and pH during experimental acid loading. The
final set of studies will evaluate the effects of two well known
ulcerogens, aspirin and bile salt, on processes which regulate cell ion
composition and whether alterations in these processes would impair the
cell's ability to neutralize or dispose of influxing H+ ions. The proposed
studies should provide, at the cellular level, a more detailed
understanding of the protective functions of the gastric surface epithelium
and of the disturbances of cell transport and permeability properties which
occur in different ulcerogenic conditions.
Effective start/end date2/1/921/31/03


  • National Institutes of Health
  • National Institutes of Health: $200,015.00
  • National Institutes of Health: $218,560.00
  • National Institutes of Health: $212,192.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $120,380.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $144,130.00
  • National Institutes of Health


Gastric Mucosa
Gastric Parietal Cells
Sodium-Potassium-Chloride Symporters
Gastric Fundus
Bile Acids and Salts
Necturus maculosus
Wounds and Injuries
Ammonium Compounds
Mucous Membrane
Cell Membrane