Abstract
Gastric acid secretion has been sometimes inadequately expressed as pH value rather than amount of gastric H+ secreted per unit time. Gastric acid secretion is regulated by endocrine, paracrine and neurocrine signals via at least three messenger pathways: gastrin-histamine, CCK-somatostatin, and neural network. These pathways have been largely validated and further characterized by phenotyping a series of knockout mouse models. The complexity of gastric acid secretion is illustrated by both expected and unexpected phenotypes of altered acid secretion. For examples, in comparison with wild-type mice, gastrin and CCK double knockout and somatostatin receptor subtype 2 (SSTR2) knockout mice displayed a shift in the regulation of ECL cells from somatostatin-SSTR2 pathway to galanin-Gal1 receptor pathway; a shift in the regulation of parietal cells from gastrin-histamine pathway to vagal pathway; and a shift in the CCK2 receptors on parietal cells from functional silence to activation. The biological function of glycine-extended gastrin in synergizing gastrin-17 has been revealed in gastrin knockout mice. The roles of gastric acid secretion in tumorigenesis and ulceration have not been fully understood. Transgenic hypergastrinemic INS-GAS mice developed a spontaneous gastric cancer, which was associated with an impaired acid secretion. Gastrin knockout mice were still able to produce acid in response to vagal stimulation, especially after H. pylori infection. Taken together, phenotyping of a series of genetically engineered mouse models reveals a high degree of complexity of gastric acid secretion in both physiological and pathophysiological conditions.
Keywords: Acid secretion, CCK, gastrin, knockout mice, receptors, somatostatin, stomach
Current Pharmaceutical Design
Title: Complexity of Gastric Acid Secretion Revealed by Targeted Gene Disruption in Mice
Volume: 16 Issue: 10
Author(s): Duan Chen and Chun-Mei Zhao
Affiliation:
Keywords: Acid secretion, CCK, gastrin, knockout mice, receptors, somatostatin, stomach
Abstract: Gastric acid secretion has been sometimes inadequately expressed as pH value rather than amount of gastric H+ secreted per unit time. Gastric acid secretion is regulated by endocrine, paracrine and neurocrine signals via at least three messenger pathways: gastrin-histamine, CCK-somatostatin, and neural network. These pathways have been largely validated and further characterized by phenotyping a series of knockout mouse models. The complexity of gastric acid secretion is illustrated by both expected and unexpected phenotypes of altered acid secretion. For examples, in comparison with wild-type mice, gastrin and CCK double knockout and somatostatin receptor subtype 2 (SSTR2) knockout mice displayed a shift in the regulation of ECL cells from somatostatin-SSTR2 pathway to galanin-Gal1 receptor pathway; a shift in the regulation of parietal cells from gastrin-histamine pathway to vagal pathway; and a shift in the CCK2 receptors on parietal cells from functional silence to activation. The biological function of glycine-extended gastrin in synergizing gastrin-17 has been revealed in gastrin knockout mice. The roles of gastric acid secretion in tumorigenesis and ulceration have not been fully understood. Transgenic hypergastrinemic INS-GAS mice developed a spontaneous gastric cancer, which was associated with an impaired acid secretion. Gastrin knockout mice were still able to produce acid in response to vagal stimulation, especially after H. pylori infection. Taken together, phenotyping of a series of genetically engineered mouse models reveals a high degree of complexity of gastric acid secretion in both physiological and pathophysiological conditions.
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Cite this article as:
Chen Duan and Zhao Chun-Mei, Complexity of Gastric Acid Secretion Revealed by Targeted Gene Disruption in Mice, Current Pharmaceutical Design 2010; 16 (10) . https://dx.doi.org/10.2174/138161210790945904
DOI https://dx.doi.org/10.2174/138161210790945904 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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