Functional analyses of gastric mucosa using mice deficient in both histamine H_2 receptor and CCK_B/gastrin receptor

为了阐明胃粘膜中胃泌素和组胺H_2受体的作用，制备并分析了两者缺陷的小鼠。双无效小鼠表现出胃粘膜萎缩，显著的高胃泌素血症和较高的胃pH值比胃泌素受体无效小鼠，这是没有反应，甚至卡巴胆碱。比较10周龄野生型、H_2受体缺失、胃泌素受体缺失和双缺失小鼠的胃粘膜，揭示了这些受体在胃粘膜中的独特作用。产酸功能受损是壁细胞变小、颈粘液细胞数量和粘液含量增加的继发因素，H_2受体参与了主细胞的成熟。在双无效和胃泌素受体无效的小鼠，尽管胃粘膜萎缩，表面粘液细胞显着增加，与胃泌素无效的小鼠。除胃泌素-17外的其他胃泌素基因产物可能与H_2受体无关地负责增加。因此，不同的GPCR影响从胃粘膜中的共同干细胞分化成不同的细胞。

To decipher the roles of gastrin and histamine H_2 receptors in gastric mucosa, mice deficient in both were generated and analyzed. Double-null mice exhibited atrophy of gastric mucosae, marked hypergastrinemia and higher gastric pH than gastrin receptor-null mice, which was unresponsive even to carbachol. Comparison of gastric mucosae from 10-week-old wild type, H_2 receptor-null, gastrin receptor-null and double-null mice revealed unique roles of these receptors in gastric mucosa. While small parietal cells and increases in the number and mucin contents of mucous neck cells were secondary to impaired acid production, H_2 receptor was responsible for chief cell maturation. In double-null and gastrin receptor-null mice, despite gastric mucosal atrophy, surface mucous cells were significantly increased, in contrast to gastrin-null mice. Other gastrin-gene product than gastrin-17 may be responsible for the increase independently of the H_2 receptor. Thus, different GPCRs affect differentiation into different cells derived from common stem cells in gastric mucosa.