| Project/Area Number |
05807069
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | OSAKA MEDICAL COLLEGE |
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Principal Investigator |
TAMAI Hiroshi Osaka, Medical, College of medicine, lectuer, 医学部, 講師 (30179874)
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| Co-Investigator(Kenkyū-buntansha) |
MINO Makoto Osaka, Medical, College of medicine, professor, 医学部, 教授 (70090206)
OGIHARA Tohru Osaka, Medical, College of medicine, assistant, 医学部, 助手 (00211128)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Monochloramine / short-circuit current / Ca / Ca / NH_2Cl / ラット腸上皮 / GSH |
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| Research Abstract |
Neutrophil-derived oxidants may be involved in inflammatory bowel disease (IBD). Stable oxidants formed by halogenation of primary amines (e.g., monochloramine, NH_2Cl) are extremely potent and may be major importance in the pathophysiological response in IBD.NH_2Cl increases short-circuit current (lsc) in a concentration-dependent manner on muscle-stripped rat colon. At concentrations found in inflamed tissues, NH_2Cl increases lsc probably by stimulating release of arachidonate metabolites and neurotransmitter (s). NH_2Cl also may act directly on the epithelial cell to stimulate lsc and evoke Cl^- secretion. To clarify this direct effect of NH_2Cl, we conduct the next experiment of cultured T84 monolayrs. NH_2Cl increases lsc in T84 monolayrs dose-dependently. ^<36>Cl flux studies demonstrated taht NH_2Cl increases serosa-to-mucosa flux of Cl. lsc responses to NH_2Cl are dependent on medium calcium. As demonstrated in fura-2-loaded T84 cells, NH_2Cl increases free cytosolic calcium by influx of extra-cellular Ca^<2+> and by release of Ca^<2+> from endogenous stores. However, NH_2Cl had no effect on phosphatidylinositol metabolism or cyclic nucleotide levels. Serosal exposure to the antioxidant glutathione (0.25mM), 5 min before NH_2Cl (50muM) addition, decreased the maximal effect of 50muM NH_2Cl on lsc. Pretreatment with 0.1 mM diamide shortened the lag period before the increase in lsc in response to NH_2Cl, but it did not affect the maximal increase in lsc.
In vitro and in intact mucosa, NH_2Cl in part activates neurotransmitter release which stimulates active secretion. Our studies support the hypothesis that a second delayd phase of NH_2Cl-stimulated secretion results from a direct action of NH_2Cl on epithelial ion transport. Moreover, these results support a role for epithelial cell thiols in NH_2Cl-stimulated electrolyte secretion by rat colon.
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