| Project/Area Number |
12670530
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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 |
Gastroenterology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
SHIMAMOTO Chikao Osaka Medical College Faculty of Medicine Associate Professor, 医学部, 助教授 (00211285)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Kumiko Osaka Medical College Faculty of Medicine Research Assistant, 医学部, 専攻医
大西 敦子 大阪医科大学, 医学部, 専攻医
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| Project Period (FY) |
2000 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | mucin / exocytosis / NSAID / prostaglandin / acetylcholine / cAMP / priming / fusion / Ca^<2+> / isoproterenol / prostagland in E_2 / prostanoid receptor |
|---|
| Research Abstract |
Direct effects of indomethacin or aspirin on Ca^<2+>-regulated exocytosis activated by acetylcholine (ACh, 10 pM) were studied in guinea pig antral mucous cells using video optical microscopy. Indomethacin or aspirin partially inhibited Ca^<2+>-regulated exocytotic events activated by ACh in a dose dependent manner. Similar inhibition was induced by a PKA inhibitor (10 pM H-89), and prostaglandin E_2 (PGE_2, 1 μM) prevented the indomethacin-induced inhibition. Our previous report showed PGE_2 effects were mediated via cAMP accumulation. Indomethacin is a well known inhibitor of cycloxygenase (COX) which inhibits PGE_2 production. Thus, the indomethacin-induced inhibition of Ca^<2+>-regulated exocytosis is caused by reduction of cAMP accumulation. Moreover, indomethacin also partially inhibited Ca^<2+>-regulated exocytotic events activated by ionomycin. These observations indicate that indomethacin decreased Ca^<2+>-regulated exocytotic events by inhibiting PGE_2 synthesis, which stimulated by Ca^<2+>-activated COX.
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