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

Research Project

Project/Area Number 15390227
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

ISHIKAWA Takashi  The University of Tokyo, Health Service Center, Lecturer, 保健センター, 講師 (50202958)

Co-Investigator(Kenkyū-buntansha) FUKUSHIMA Yasushi  The University of Tokyo, Faculty of Medicine, Medical Stuff, 医学部附属病院, 医員
TATEISHI Keisuke  The University of Tokyo, Faculty of Medicine, Medical Stuff, 医学部附属病院, 医員
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥7,800,000 (Direct Cost: ¥7,800,000)
Keywordshistamine 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
Research Abstract

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.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (11 results)

All 2004 2003 Other

All Journal Article (8 results) Publications (3 results)

  • [Journal Article] Unique roles of G protein-coupled histamine H2 and gastrin receptors in growth and differentiation of gastric mucosa2004

    • Author(s)
      福嶋康之 他
    • Journal Title

      European Journal of Pharmacology 502/3

      Pages: 243-252

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] H2受容体の発見と潰瘍治療薬開発史2004

    • Author(s)
      福嶋康之 他
    • Journal Title

      総合臨床 53/12

      Pages: 3000-3005

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] ヒスタミンH2、ガストリン受容体欠損マウスを用いた病態研究2004

    • Author(s)
      福嶋康之 他
    • Journal Title

      日本臨床 62/3

      Pages: 551-555

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Unique roles of G protein-coupled histamine H2 and gastrin receptors in growth and differentiation of gastric mucosa.2004

    • Author(s)
      Fukushima Y, Matsui T, Saitoh T, Ichinose M, Tateishi K, Shindo T, Fujishiro M, Sakoda H, Shojima N, Kushiyama A, Anai M, Ono H, Oka M, Shimizu S, Nagai R, Kurihara H, Ishikawa T, Asano T, Omata M.
    • Journal Title

      Eur J Pharmacol 502

      Pages: 243-252

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Structural and functional characterization of gastric mucosa and central nervous system in histamine H(2) receptor-null mice2003

    • Author(s)
      福嶋康之 他
    • Journal Title

      European Journal of Pharmacology 468/1

      Pages: 47-58

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells2003

    • Author(s)
      福嶋康之 他
    • Journal Title

      Digestion 68/2-3

      Pages: 145-152

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells.2003

    • Author(s)
      Fukushima Y, Ishikawa T, Saitoh T, Tateishi K, Ogihara T, Fujishiro M, Shojima N, Honda M, Kushiyama A, Anai M, Sakoda H, Ono H, Onishi Y, Otsuka H, Katagiri H, Nagai R, Omata M, Asano T.
    • Journal Title

      Digestion 68

      Pages: 145-152

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Structural and functional characterization of gastric mucosa and central nervous system in histamine H(2) receptor-null mice.2003

    • Author(s)
      Fukushima Y, Shindo T, Anai M, Saitoh T, Wang Y, Fujishiro M, Ohashi Y, Ogihara T, Inukai K, Ono H, Sakoda H, Kurihara Y, Honda M, Shojima N, Fukushima H, Haraikawa-Onishi Y, Katagiri H, Shimizu Y, Ichinos M, Ishikawa T, Omata M, Nagai R, Kurihara H, Asano T.
    • Journal Title

      Eur J Pharmacol 468

      Pages: 47-58

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Fukushima Y, et al.: "Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells."Digestion. 68. 145-152 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 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)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanaka Y, et al.: "Congenital absence of portal vein with multiple hypervascular nodular lesions in the liver."J Gastroenterol. 38. 288-294 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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