| Project/Area Number |
08671291
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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 | Kumamoto University |
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Principal Investigator |
NONOGUCHI Hiroshi Kumamoto Univ Sch of Med.Associate Professor, 医学部・附属病院, 講師 (30218341)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | edema / vasopressin / V1a receptor / V2 receptor / mRNA / collecting duct / 脱水 / プロスタグラデイン E2 / V1a受容体 / V2受容体 / competitive PCR / プロスタグランディン E2 / 集合尿細管 / 杭利尿ホルモン / 慢性腎不全 / RT-PCR |
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| Research Abstract |
This study was designed to investigate the mechanisms and therapy of refractory renal edema. We have focused on V1a and V2 vasopressin (ADH) receptors. WE have already reported the V2 receptor is localized in basolateral membrane of distal nephron segments. Therefore, we first investigated intranephron localization of V1a receptor. The results showed that V1a receptor is located in glomeruli and in luminal membrane of collecting ducts.
Next, the mechanisms of V2 receptor (V2R) mRNA expression in inner medullary collecting ducts (IMCD) were investigated. V2R mRNA is known to downregulate in dehydration. However, vasopressin and hyperosmolality, both are known to increase in dehydration, stimulated V2R mRNA expression in vitro. There is some inhibitory factor on V2R mRNA expression in dehydration. One of the canditate is prostaglandin E2 (PGE2). PGE2 is known to decrease ADH-dependent cAMP generation in collecting ducts. PGE2 inhibited ADH- and hyperosmolality-stimulated V2R mRNA expression. Thus, increased PGE2 generation seems to inhibit V2R mRNA expression in dehydration. We are still investigating the role of PGE2 to know the mechanisms of diuresis. The final goal of our study is to use our knowledge for the therapy of renal edema.
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