Differentiation of the Gastric Mucosa I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes

Abstract

Many physiological functions of the stomach depend on an intact mucosal integrity; function reflects structure and vice versa. Histamine in the stomach is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like (ECL) cells, and released in response to gastrin, acting on CCK2 receptors on the ECL cells. Mobilized ECL cell histamine stimulates histamine H2 receptors on the parietal cells, resulting in acid secretion. The parietal cells express H2, M3, and CCK2 receptors and somatostatin sst2 receptors. This review discusses the consequences of disrupting genes that are important for ECL cell histamine release and synthesis (HDC, gastrin, and CCK2 receptor genes) and genes that are important for “cross-talk” between H2 receptors and other receptors on the parietal cell (CCK2, M3, and sst2 receptors). Such analysis may provide insight into the functional significance of gastric histamine.