Die Belegzelle des Magens: diametrale Bedeutung für die gastroösophageale Refluxkrankheit (GERD)

Abstract

BACKGROUND: The gastric parietal cell (also called oxyntic cell) is a remarkable physiological entity in view of its regulation and participation in digestion, but also as an exemplary model for its exaggerated biophysical and cell biological processes. Moreover, the ability to pharmacologically control parietal cell activity has proven enormous value in treating a number of pathological conditions. METHODS: This review summarizes what is known about some of the most important physiological activities of the gastric parietal cell. RESULTS: Clues from differences in phenotype between resting and actively secreting cells provide a morphological basis for the massive biological process of intracellular membrane recycling, and explain the regulation by recruitment of the primary proton pump, H,K-ATPase, to the secretory surface. The large changes in membrane surface area require the sub-structural support of the filamentous actin cytoskeleton, which together with a dynamic membrane-cytoskeleton linker protein, known as ezrin, offer the scaffold for large membrane elaborations as well as required plasticity of the resulting microvillar extensions. Studies on basic protein/glycoprotein structure of H,K-ATPase have offered autoprotective mechanisms for the proton pump, and suggest the possibility that similar features in other gastric apical surface proteins may provide a molecular basis to why the stomach does not digest itself. An adjacent anatomical area, the esophagus, does not have the power to resist autodigestion resulting from backflux of gastric (and duodenal) juices; this is the pathological condition called gastroesophageal reflux disease, GERD. Interestingly, GERD related metaplastic changes in the distal esophageal epithelium ultimately result in one of two epithelial phenotypes: one called cardio-oxyntic mucosa, rarely leading to more serious consequences; and the other intestinal mucosa, characterized by goblet cells and having increased probability for progression to dysplasia and adenocarcinoma. CONCLUSIONS: Factors that promote lower esophageal metaplasia and dysplasia have interesting similarities with atrophic gastritis and glandular metaplasia of the gastric mucosa, i.e., intestinalization indicative of adenocarcinoma. These comparisons are discussed for the parietal cell in an unusual environment.