Future directions for reductionistic research in gastric secretion and defense.

Our theme centers on the complex processes that constitute and regulate the function of the gastric mucosa. Although some investigators promote the critical importance of a given element, such as acid, blood flow, or mucus, it is clear that both gastric secretory function and mucosal defense and repair mechanisms are multifactorial and are regulated by redundant control circuits. While it is true that critical studies can be performed in vivo with intact mucosa, at the same time it is frequently difficult, using these methods, to define the specific cellular elements involved in the regulation of secretion, defense, and repair. We now recognize that ulcer disease does not occur simply when this balance is thrown off. To the contrary, ulcer disease commonly occurs when the normal mucosal mechanisms are perturbed by Helicobacter pylori-associated gastro-duodenitis or nonsteroidal anti-inflammatory drugs. In the absence of such perturbation, the redundancy of the regulatory mechanisms underlying gastric secretion and the multiple lines of defense and healing would render ulcer disease rare indeed.