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2000 Fiscal Year Final Research Report Summary

Effects of acid inhibitors on progression of gastric atrophy and development of gastric cancer in Helicobacter pylori-infected gastric mucosa.

Research Project

Project/Area Number 10670450
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionUNIVERSITY OF TSUKUBA

Principal Investigator

YANAKA Akinori  University of Tsukuba Institute of Clinical Medicine assistant professor, 臨床医学系, 講師 (80272201)

Project Period (FY) 1998 – 2000
KeywordsHelicobacter pylori / gastritis / gastric atrophy / ammonia / apoptosis / H2-receptor antagonist / proton pump inhibitor
Research Abstract

Aims : H.pylori (Hp) produces high concentrations of ammonia by high urease activity. The present study was conducted to clarify the mechanisms by which ammonia disrupts gastric mucosal barrier function and induces apoptosis of gastric epithelial cells.
Methods : 1. In vitro study : (1) Effects of ammonia (NH4Cl) on apoptosis of GSM06 cells, epithelial cell line derived from mice gastric mucosae were examined in vitro. (2) Effects of NH4Cl on electrophysiology and morphology of intact sheets of gastric fundic mucosae were examined in vitro. 2. In vivo study : Effects of prolonged use of acid inhibitors (H2-blocer, PPI) on gastric inflammation and gastric atrophy were examined in C57/BL6 mice infected with Hp.
Results : 1. In vitro study (1) NH4Cl induced apoptosis of GSM06 cells, an effects augmented at high ambient pH.(2) NH4Cl decreased in potential difference and resistance, and induced cytoplasmic vacuolation in gastric glands especially at high luminal pH.2. In vivo study : Prolonged use of acid inhibitors such as proton pump inhibitors or H2-blockers exacerbated gastritis and apoptosis, accelerated atrophy in body, but not in antrum, in Hp-positive, but not in Hpnegative mice.
Conclusions : Prolonged acid inhibition exacerbates body gastritis, enhances apoptosis of gastric gland, and accelerates body atrophy, in Hp-infected gastric body mucosa effects mediated by conversion of ammonia from NH4^+ to NH3 during acid inhibition.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 鈴木英雄,谷中昭典,武藤弘 他: "Helicobacter Pyloriによる胃粘膜障害のメカニズム(第2報)"Ulcer Research. 25. 266-270 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木英雄,谷中昭典,武藤弘 他: "Helicobacter Pyloriによる胃粘膜上皮細胞傷害のメカニズム(第3報)"Ulcer Research. 26. 48-52 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki,Hidco,Yancka,Akinorim,Muto,Hiroshi: "Luminal ammonia retards restitution of injured guinea pig gastric mucosa in vitro"American Journal of Physiology. 279. G107-G117 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 谷中昭典,鈴木英雄,武藤弘: "H.Pylori由来空胞化毒素(UacA)の胃粘膜上皮細胞(GSM06)の細胞間結合に及ぼす影響,及びteprenoneのVacA結抗作用"Ulcer Research. 27. 4-8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木英雄,谷中昭典,武藤弘 他: "アンモニアによる胃粘膜上皮細胞アポトーシスのメカニズム"Ulcer Research. 27. 157-160 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 谷中昭典,鈴木英雄,武藤弘 他: "胃酸分泌抑制剤の一長期投与p-H.prlori感染マウスにおける胃粘膜萎縮進展に及ぼす影響"胃分泌研究会誌. 32. 47-50 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hideo Suzuki, Akinori Yanaka, Hiroshi Muto.: "Effects of luminal and/or serosal ammonia on protection and repair of guinea pig gastric mucosa in vitro."Ulcer Research. 25. 266-270 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hideo Suzuki, Akinori Yanaka, Hiroshi Muto.: "Effects of ammonia and monochloramine on gastric mucosal barrier at different luminal pH."Ulcer Research. 26. 48-52 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hideo Suzuki, Akinori Yanaka, Hiroshi Muto.: "Luminal ammonia retards restitution of injured guinea pig gastric mucosa in vitro."American Journal of Physiology. 279. G107-G117 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akinori Yanaka, Hideo Suzuki, Hiroshi Muto.: "Helicobacter pylori vacuolating cytotoxin (Vac A) Increases paracellular permeability across the gastric mucosae, effects prevented by a heat shock protein inducer, tetraprenylacetone."Ulcer Research. 27. 4-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hideo Suzuki, Akinori Yanaka, Hiroshi Muto.: "The mechanism of gastric mucosal apoptosis induced by ammonia."Ulcer Research. 27. 157-160 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akinori Yanaka, Hideo Suzuki, Hiroshi Muto.: "Prolonged acid inhibition accelerated gastric body Atrophy in H.pylori infected c57BL/6 mice in vivo."Journal of Japanese Gastric Secretion Research. 32. 47-50 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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