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DETERMINATION OF ENDOGENOUSLY PRODUCED NITRIC OXIDE (NO) IN RAT STOMACH : CYTOPROTECTIVE ROLE OF NO

Research Project

Project/Area Number 11470497
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionINSTITUTE FOR LIFE SUPPORT TECHNOLOGY (ILST), YAMAGATA PUBLIC CORPORATION FOR THE DEVELOPMENT OF INDUSTRY

Principal Investigator

YOSHIMURA Tetsuhiko  ILST, LAB.OF APPLIED BIOMEDICINAL CHEM.CHIEF SENIOR RESEARCHER, 生物ラジカル研究所, 首席研究員 (70271517)

Co-Investigator(Kenkyū-buntansha) KISO Yoshinobu  SUNTORY LTD., INST.FUNDAMENTAL RES.SENIOR RESEARCHER, 基礎研究所, 主席研究員
KATO Katsuaki  TOHOKU UNIV.SCH.MED., INTERNAL MED.ASSISTANT PROF., 医学部, 助手 (30292212)
FUIII Satoshi  ILST, YAMAGATA TECHNOPOLIS FOUNDATION DIVISION OF BIOINORGANIC CHEMISTRY RESEARCHER, 研究員 (80271518)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥9,000,000 (Direct Cost: ¥9,000,000)
KeywordsNITRIC OXIDE / ENDOGENOUSLY PRODUCED NITRIC OXIDE / NO IN STOMACH / CHAMBERED STOMACH / NITRITE / NITRATE / S-NITROSOTHIOL / DINITROSYL DITHIOLATO IRON COMPLEX / チャンバード・スタマック法 / チャンバート・スタマック法
Research Abstract

Nitric oxide (NO) is biologically synthesized in stomach by three forms of nitric oxide synthase (NOS). Nitrite in saliva derived from dietary nitrate is chemically reduced to NO under the acidic conditions in the stomach. Thus, gastrointestinal tracts are highly exposed to NO derived from both endogenous and exogenous origins. Recently, endogenously synthesized NO in stomach has been demonstrated to exert physiological and pathophysiological effects on gastric mucosal blood flow, acid and mucus secretion, gastric motility, and regulates mucosal defense and injury. In this study we investigated the roles of NO on ethanol-induced gastric mucosal injury in rats. Under urethane anesthesia, a rat stomach was mounted on an ex vivo chamber ; saline and then aqueous ethanol (43%) solutions were perfused. NO production in stomach tissues was analyzed by spin trapping technique combined with electron paramagnetic resonance spectroscopy. Nitrite and nitrate (NOx) in the luminal fluid were determined by the Griess-reaction assay with HPLC.Gastric mucosal blood flow, luminal pH, gastric mucosal potential difference, and area of the macroscopic mucosal injury were evaluated with/without preadministration of NOS inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME). Preadministration of L-NAME aggravated mucosal damage and suppressed increase of mucosal blood flow. In conclusion, endogenously produced NO plays an important role in the protection against ethanol-induced gastric injury via regulation of gastric mucosal blood flow. Further, we investigated the physiological activities and in vivo distribution of dinitrosyl dithiolato iron complex (DNIC), which has been recognized as one of endogenous NO donor molecules. A combination of ex vivo and in vivo EPR spectrometry made it possible to reveal that DNIC not only possesses an excellent membrane-permeability but also has a markedly high affinity for the liver and kidney.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] 菅田英明: "エタノール胃粘膜損傷(ラット)におけるNO測定とNOの生理作用"磁気共鳴と医学. 12(印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 上野孝治: "In vivo distribution and behavior of dinitrosyldithiolato iron complex in the abdomen of mouse"Free Radic.Res.. 31. 525-534 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 上野孝治: "The physiological activity and in vivo distribution of dinitrosyl dithiolato iron complex"Jpn.J.Physiol.. 82. 95-101 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 藤井敏司: "Reaction of nitric oxide with the ison (III) complex of N-(dithiocarboxy) sarcosine : a new type of reductive nitrosylation involving iron (IV) as an intermediate"J.Chem.Soc.Dalton Trans.. 3310-3315 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 藤井敏司: "Detection and imaging of endogenously produced nitric oxide with electron paramagnetic resonance spectroscopy"Antiox.Redox Sig.. 2. 879-901 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 吉村哲彦: "生体内NOの化学"血圧. 6. 471-477 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 吉村哲彦 編著: "生体内一酸化窒素(NO)実験プロトコール"共立出版株式会社. 288 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Ueno, Y.Suzuki, S.Fujii, A.F.Vanin, T.Yoshimura: "In vivo distribution and behavior of dinitrosyl dithiolato iron complex in the abdomen of mouse"Free Radical Res.. 31. 525-534 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Fujii, K.Kobayashi, S.Tagawa, T.Yoshimura: "Reaction of nitric oxide with iron (III) complex of N-(dithiocarboxy)sarcosine : A New type of reductive nitrosylation involving the iron (IV) as an intermediate"J.Chem.Soc.Dalton Trans.. 3310-3315 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Inoue, T.Akaike, Y.Miyamoto, M.Otagiri, S.Suzuki, T.Yoshimura, H.Maeda: "Nitrosothiol formation catalyzed by ceruloplasmin"J.Biol.Chem. 274. 27069-27075 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Ueno, T.Yoshimura: "The physiological activity and in vivo distribution of dinitrosyl dithiolato iron complex"Jpn.J.Pharmacol.. 82. 95-101 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Fujii, T.Yoshimura: "A new trend in iron-dithiocarbamate complexes : As an endogenous NO trapping agent"Coordin.Chem.Rev.. 199. 89-99 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Fujii, T.Yoshimura: "Detection and imaging of endogenously produced nitric oxide with electron paramagnetic resonance spectroscopy"Antiox.Redox Sig.. 2. 879-901 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Fujii, K.Kobayashi, S.Tagawa, T.Yoshimura: "Novel redutive nitrosylation realized in Fe (III) complexes having sulfur-containing ligands"J.Inorg.Biochem.. 74. 132 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 菅田英明: "エタノール胃粘膜損傷(ラット)におけるNO測定とNOの生理作用"磁気共鳴と医学. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 上野孝治: "内因性NO・チオレート鉄錯体のNO基供与性に関するEPRによる検討"磁気共鳴と医学. 11. 83-86 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 藤井敏司: "A new trend in iron-dithiocarbamate complexes : as an endogenous NO trapping"Coordination Chemistry Reviews. 198. 89-99 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 藤井敏司: "Reaction of nitric oxide with the iron(III) complex of N-(dithiocarboxy) sarcosine : a new type of reductive nitrosylation involving iron(IV) as an intermedaite"Journal of Chemical Society. Dalton Transaction. 3310-3315 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 藤井敏司: "Detection and imaging of endogenously produced nitric oxide with electron paramagnetic resonance spectroscopy"Antioxidants and Redox Signaling. 879-901 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉村哲彦 編著: "生体内一酸化窒素(NO)実験プロトコール"共立出版株式会社. 288 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Ueno: "In vivo distribution and behavior of dinitrosyl dithiolato iron complex in the abdomen of mouse"Free Radical Res.. 31. 525-534 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Ueno: "The physiological activity and in vivo distribution of dinitrosyl dithiolato iron complex"Jpn.J.Pharmacol.. 82. 95-101 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Inoue: "Nitrosothiol formation catalyzed by ceruloplasmin"J.Biol.Chem.. 274. 27069-27075 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 上野孝治: "内因性NOドナー(NOチオレート鉄錯体)のマウス腹部における分布、動態に関する研究"G.I.Research. 7. 321 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉村哲彦: "生体内NOの化学"血圧. 6. 471-477 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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