The long-term objectives of this proposal are to define the conditions which cause superficial injury to the gastric mucosa and to elucidate (characterize) in detail the ensuing mucosal repair or restitution process which rapidly reepithelializes the damaged surface.
The specific aims are to further our understanding of the cellular mechanisns involved in restitution and to correlate the time course of damage and repair with changes in mucosal electrophysiology, ultrastructure, and transmucosal flux. The tissue preparations to be employed are the Ussing chambered, stripped guinea pig gastric mucosa and the in vivo ligated rat stomach. The mucosa will be treated with various agents that may enhance or retard restitution and the epithelial tissues will be analyzed for microfilament and polymerization and organization, cell movement, adhesion, and junction formation. Mucosal potential differences and resistances are measured in the in vitro preparations as well as flux of large particles such as albumin and hemoglobin; intermediate size molecules such as sucrose and mannitol; and sodium and chloride ions. Ligated stomachs of intact rats will be filled with concentrated ethanol and the efflux of ethanol as well as influx of diluting fluids will be measured during gastric injury and restitution. Related studies are aimed at determining the actual extent and concentration of ethanol penetration into the in vivo mucosa and the maximum tolerance of gastric cells to ethanol permeation. The tracers which include hemoglobin, peroxidase, ethanol, mannitol, sodium and chloride will be quantitatively measured by chemical, enzymatic, or radioisotopic methods. These studies are closely related to the prevelant problem of gastric ulcer prevention and healing. Mucosal restitution is a recently acknowledged concept and relatively little of the basic biology of this process has been elucidated.
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