2004 Fiscal Year Final Research Report Summary
Investigation on electrolyte transport in the renal tubule by using knockout mice
| Project/Area Number |
14571031
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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 | Jichi Medical School |
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Principal Investigator |
MUTO Shigeaki Jichi Medical School, Department of Nephrology, Associate Professor, 医学部, 助教授 (40190855)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Yukio Jichi Medical School, Department of Nephrology, Assistant Professor, 医学部, 講師 (00285777)
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| Project Period (FY) |
2002 – 2004
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| Keywords | P-glycoprotein / proximal tubule / Na / H exchanger / mannitol / urea / regulatory volume increase |
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| Research Abstract |
The role of P-glycoprotein(P-gp) in cell volume regulation and the involvement of the basolateral Na/H exchange(NHE) in the P-gp-induced cell volume regulation were examined in isolated nonperfused proximal tubule S2 segments from wild-type (WT) mice and those (KO) in which both the mdrla and mdrlb genes were knocked out. The results were in the following :
1.In the mouse proximal tubule, P-gp modulates regulatory volume increase(RVI) during hyperosmotic mannitol stress, but not regulatory volume decrease during hyposmotic stress.
2.The basolateral membrane NHE partly contributes to the P-gp induced modulation of RVI under the hyperosmotic stress.
3.In both groups of the tubules exposed to hyperosmotic urea, the reduction in cell volume was smaller and transient, tubules returning to their control volume immediately.
4.P-gp-induced modulation of RVI during the exposure to the hyperosmotic mannitol solution is mediated via PKC.
5.The microtubule, microfilament, and wortmannin-sensitive, LY 294002-insensitive phosphatidylinositol 3-kinase contribute to the PKC-induced RVI.
6.In the absence of P-gp activity, the hyperosmotic mannitol activates basolateral NHE via PKC, whereas in the presence of P-gp activity, it does not.
7.The hyperosmotic urea activates basolateral NHE via tyrosine kinase in the proximal tubules from both WT and KO mice.
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