| Project/Area Number |
09672224
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Hiroshima Prefectural University (1998)
Osaka University (1997) |
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Principal Investigator |
MUTO Norio Hiroshima Prefectural University, 生物資源学部, 教授 (30112642)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Ascorbic acid / Gastric ascorbic acid secretion / Nitrosoamine / Environmental factor / Gastrointestinal disorder / アスコルビン酸 / コレシストキニン / 喫煙 |
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| Research Abstract |
The mechanism of gastric ascorbate secretion was investigated in the perfused rat stomach. Among various peptide hormones examined, cholecystokinin octapeptide (CCK-8) potently stimulated gastric ascorbate secretion in a dose-dependent manner, but others showed no effect. This stimulation by CCK-8 was apparently abolished by a specific CCK receptor antagonist, proglumide, indicating that gastric ascorbate secretion is physiologically regulatedby humoral factors as well as nervous system. In addition, CCK-8-induced gastric ascorbate secretion was Inhibited by an intravenous administration of nicotine at a dose of 1mug/kg and it was more effectively depressed by cotinine at a dose of 15 mug/kg. These findings suggest that cigarette smoke may reduce the ascorbic acid secretory response in human stomach.
Further investigation to solve the mechanism of gastric ascorbic acid secretion was carried out in in vitro cell culture system. The ascorbic acid release from a primary culture of rat gastric mucosal cells was effectively stimulated by CCK-8 and carbachol. We also demonstrated an active transport of ascorbic acid in both intestinal epithelial cells and aortic endothelial cells. These results indicate that endogenous ascorbic acid is secreted from blood to gastric lumen through its transport between these gastric mucosal cells.
To clarify the physiological role of gastric ascorbate secretion system, the effect of endogenous ascorbic acid on the Inhibition of nitrosoamine formation was evaluated. The formation of nitrosothioproline was efficiently inhibited during the fasting period and the decreasing amount of gastric ascorbic acid was recovered by a continuous secretory response.
These findings strongly indicate that ascorbic acid secreted in the stomach functions as a predominant antioxidant for the self-defense and that this secretory response is crossly associated with the onset of various gastrointestinal mucosal disorders.
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