| Project/Area Number |
11470497
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | INSTITUTE FOR LIFE SUPPORT TECHNOLOGY (ILST), YAMAGATA PUBLIC CORPORATION FOR THE DEVELOPMENT OF INDUSTRY |
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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)
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| 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)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| 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)
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| Keywords | NITRIC 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 |
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| 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.
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