| Project/Area Number |
15590641
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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 | Shiga University of Medical Science |
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Principal Investigator |
TSUJIKAWA Tomoyuki Shiga University of Medical Science, Internal Medicine, assistant professor, 医学部, 助手 (80273407)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | IBS / serotonin / AQP3 / serotonin receptor / natriuretic peptides / 5-HT3 receptor / アクアポリン / 過敏性腸症候群 |
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| Research Abstract |
Some serotonin receptor antagonists have been used as a therapy for irritable bowel syndrome. The mechanism of this action was thought to control intestinal movement via down regulation of serotonin in the intestinal neuron. We reported that the expression of AQP3 in cultured human colonic epithelial cells HT-29 was upregulated by vasoactive intestinal polypeptide. Although Ht-29 cells express 5-HT2a,5-HT3 and 5-HT4 receptors, the addition of serotonin did not alter the expression of AQP3 mRNA. To characterize the regulation of AQP3 expression by atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP), we studied mRNA expression by Northern blotting, protein expression by Western blotting and DNA binding activity by electrophoretic mobility shift assay(EMSA) in HT-29. We also used several inhibitors to investigate signal transduction. AQP3 mRNA was up-regulated in addition to ANP (more than 100 nM) and BNP (more than 10 nM). The expression of AQP3 protein was enhanced at 1 hour after the addition of ANP and BNP. The combination of protein kinase-A(PK-A) and protein kinase-G(PK-G) inhibitors completely inhibited the expression of AQP3 mRNA enhanced by ANP or BNP to its basal level. The EMSA of the cyclic-AMP response element(CRE) in HT-29 cells revealed a single band. These results indicate that ANP and BNP up-regulated the expression of AQP3 mRNA and protein, and both PK-A and PK-G dependent pathways mediated this effect.
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