Analysis of molecular mechanisms regulating gastrin secretion in a histamine H2 receptor deficient mouse

众所周知，胃窦G细胞的胃泌素释放是通过H+的直接化学作用来调节的。高胃泌素血症是通过使用酸抑制剂如H2受体拮抗剂和质子泵抑制剂抑制胃酸分泌而诱导的。然而，调节胃泌素释放的确切机制尚不清楚。本实验研究了组胺H_2受体缺陷小鼠胃酸与胃泌素释放的关系。我们在组胺H2受体缺陷和野生型小鼠中建立胃瘘。我们能够进行24 pH值监测，并通过胃瘘给药酸改变胃pH值。结果表明，野生型小鼠血胃泌素水平随胃内pH值的变化而变化。在组胺H_2受体缺陷的小鼠中，胃pH值的变化不影响血中胃泌素的水平。这些结果表明，壁细胞和胃泌素释放细胞之间的某些信号转导可能刺激了胃泌素的释放。因此，我们正在计划寻找具有这种信号转导功能的候选蛋白。为此，我们进行了来自胃粘膜的每个部分的mRNA的表达筛选。我们试图找出当胃pH升高时显示出升高表达的mRNA。

It is well known that gastrin release from the antral G cell is regulated through the direct chemical effect of H+. Hypergastrinemia is induced by the suppression of gastric acid secretion using acid suppressants such as H2 receptor antagonists and proton pump inhibitors. However, the exact mechanism of regulating gastrin release has not been understood. We conducted the experiments to examine the relation of gastric acidity and gastrin release in histamine H2 receptor deficient mouse. We made gastric fistula in histamine H2 receptor deficient and wild type mice. We were able to perform 24 pH monitoring and change gastric pH by acid administration through gastric fistula in both mice. We found that the blood gastrin level varied with the changes of gastric pH in wild type mice. In histamine H2 receptor deficient mice, blood gastrin level was not influenced by the change of gastric pH. These results shown the possibility that gastrin release is stimulated by some signal transduction between parietal cells and gastsrin releasing cells. Therefore we are now planning for searching the candidate protein which possesses such signal transduction function. For this purpose, we performed an expression screening of mRNA derived from each portion of gastric mucosa. We tried to find out mRNA which shows an elevated expression when gastric pH increases.