| Project/Area Number |
06670563
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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 | Kyushu University |
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Principal Investigator |
CHIJIIWA Yoshiharu Kyushu University, Faculty of Medicine, Assistznt Professor, 医学部, 助手 (90188475)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | colon / smooth muscle cell / ANP / VIP / TRH / CRH / CCK / 実験大腸炎 |
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| Research Abstract |
We investigated the effect and the intracellular mechanism of atrial natriuretic peptide (ANP), thyrotropin releasing hormore (TRH), and corticotropin releasing hormone (CRH) on isolated cecal circular smooth muscle cells of guinea pig. Furthermore, binding assay was performed to examine the receptors of ANP and CRH.In addition, we examined cholecystokinin (CCK) receptor subtypes on these cells.
ANP stimulated NO production and subsequently induced relaxation via a receptor to which vasoactive intestinal peptide (VIP) binds.
TRH inhibited the contractile response produced by carbachol. A soluble guanylate cyclase inhibitor and an inhobitor of nitric oxide syntase significantly inhibited the relaxation produced by TRH.On the contrary, an adenylate cyclase inhibitor and a particulate guanylate cyclase inhibitor did not have any significant effect on the relaxation produced by TRH.Our findings shows that TRH has a direct inhibitory effect on the cecal circular smooth muscle cells via activation of nitric oxide synthase and soluble guanylate cyclase.
CRH inhibited the contractile response produced by CCK-8. An inhibitor of adenylate cyclase and an inhibitor of cAMP-dependent protein kinase significantly inhibited the relaxation produced by CRH.An inhibitor of particulate and soluble guanylate cyclase had no significant effect of the relaxation produced by CRH.Binding assay revealed the presence of receptors for CRH in cecal circular smooth muscle cells. These results show that CRH binds CRH receptors and induces relaxation of cecal circular smooth muscle cells via adenylate cyclase system.
Furthermore, we demonstrated the direct contractile effect of CCK-8 on cecal circular smooth muscle cells via both CCK-A and CCK-B/gastrin receptors.
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