Gastroduodenal defense

Abstract

Purpose of review: The gastroduodenum resists mucosal injury despite continuous exposure to concentrated gastric acid. The mucosal barrier consists of a preepithelial mucus HCO3- layer, intercellular tight junctions connecting the epithelial cells, and submucosal acid sensors, prostaglandins, cytokines, enteric nerves and blood flow. In the past year, study of these defensive mechanisms has revealed new insight into the observed sex differences in ulcer prevalence, the protective role of transforming growth factor, the role of serotonin in regulating HCO3- secretion, the role of mechanisms in ulcer healing, the interaction of trefoil factors with the mucus gel, the interaction of glucocorticoids with cyclooxygenase and the characterization of novel, mucosal sparing antiinflammatory agents.

Recent findings: Transforming growth factor, melatonin, serotonin, trefoil factors and H2S all enhance mucosal barrier function or accelerate ulcer healing. Newer coxibs may have safety and advantages over existing compounds. Existing nonsteroidal antiinflammatory drugs may be safer than originally thought.

Summary: The continued elucidation of basic defense mechanisms has led to the development of several new compounds designed to enhance barrier function and repair mechanisms.