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THEMES

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

¹Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; ²Deptartment of Applied Pharmacology, Doshisha Women's College, Kyoto Pharmaceutical University, Kyoto, Japan; and ³Department of Pharmacology, University of Lund, Lund, Sweden

Submitted 28 April 2006 ; accepted in final form 12 May 2006

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.

knockout mice; gastric acid secretion; oxyntic mucosal proliferation and differentiation; gastrin; histamine; gastrin receptor

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