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

使用组胺 H_2 受体和 CCK_B/胃泌素受体缺陷小鼠进行胃粘膜功能分析

• 批准号: 15390227
• 负责人: ISHIKAWA Takashi
• 金额: $ 7.87万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390227/
• 关键词: histamine H2 receptor; gastrin receptor; gastric mucosa; gastric acid secretion; ノックアウトマウス; ダブル欠損マウス

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.

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。胃泌素-17以外的其他胃泌素基因产物可能独立于H_2受体参与了这一作用。因此，不同的GPCR影响胃粘膜中常见干细胞分化为不同细胞。

项目成果

Tanaka Y, et al.: "Congenital absence of portal vein with multiple hypervascular nodular lesions in the liver."J Gastroenterol. 38. 288-294 (2003)

Tanaka Y 等人：“先天性门静脉缺失，肝脏内有多发血管丰富的结节性病变。”J Gastroenterol。

Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells

雷尼替丁对 HEK293 细胞中表达的人组胺 H2 受体的作用极早开始

• 发表时间: 2003
• 期刊: Digestion 68/2-3
• 作者: Imanaka K;Kawata S;et al.;福嶋康之 他
• 通讯作者: 福嶋康之 他

H2受容体の発見と潰瘍治療薬開発史

H2受体的发现和溃疡治疗药物的开发史

• 发表时间: 2004
• 期刊: 総合臨床 53/12
• 作者: Tsuji;N.M.;Tsutsui;H.;Seki;E.;Kuida;K.;Okamura;H.;Nakanishi;K.;Flavell;R.A.;福嶋康之 他
• 通讯作者: 福嶋康之 他

Fukushima Y, et al.: "Structural and functional characterization of gastric mucosa and central nervous system in histamine H_2 receptor-null mice"Eur J Pharmacol. 468. 47-58 (2003)

Fukushima Y 等：“组胺 H_2 受体缺失小鼠胃粘膜和中枢神经系统的结构和功能特征”Eur J Pharmacol。

Unique roles of G protein-coupled histamine H2 and gastrin receptors in growth and differentiation of gastric mucosa.

• DOI: 10.1016/j.ejphar.2004.09.013
• 发表时间: 2004-10
• 期刊: European journal of pharmacology
• 影响因子: 5
• 作者: Y. Fukushima;T. Matsui;T. Saitoh;M. Ichinose;K. Tateishi;T. Shindo;M. Fujishiro;H. Sakoda;N. Shojima;A. Kushiyama;S. Fukuda;M. Anai;Hiraku Ono;M. Oka;Y. Shimizu;H. Kurihara;R. Nagai;T. Ishikawa;T. Asano;M. Omata