| Project/Area Number |
20590973
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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 |
Kidney internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
MORIYAMA Toshiki Osaka University, 保健センター, 教授 (30283815)
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| Co-Investigator(Kenkyū-buntansha) |
KAWADA Noritaka 大阪大学, 医学部附属病院, 助教 (80437326)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | プロスタグランディンE2 / EP4受容体 / 食塩感受性 / MKP1 / p38 / Akt / Sgk1 / プロスタグランディンE_2 / EP_4受容体 / COX-1 / ENac / Sgk-1 / PKA |
|---|
| Research Abstract |
Cyclooxygenase-1 (COX-1) deficient mice are salt sensitive and polyuric under high salt diet. We have focused on the prostaglandin E2-EP4 receptor signaling pathway as a cause of these phenotypes. EP4 has been shown to enhance water absorption via cAMP production and, as anticipated, the administration of EP4 agonist : ONO-AE1-329 (EP4AG, 6x10^<-10>mol/gram body weight every one hour) in rats increased water absorption. On the other hand, sodium absorption was not enhanced by EP4AG. EP4AG (10^<-6>M) in cultured mice collecting duct (M-1) cells reduced the abundance of the phosphorylated Akt, Sgk1 and p38 proteins and increased the expression of MAP kinase phosphatase 1 (MKP1) mRNA. P38 inhibitor (BIRB796 : 10^<-5>M) reduced the protein abundance of phosphorylated Akt and Sgk-1, which could be a counteracting mechanism to cAMP-mediated sodium absorption. In conclusion, EP4AG can be an effective agent as a mediator for the
renal tubular water and electrolyte transports.
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