Elucidation of transport mechanism of NHE3 for novel therapeutic target in chronic kidney disease.
| Project/Area Number |
17K12904
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Eating habits
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| Research Institution | University of Shizuoka |
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Principal Investigator |
Ishizuka Noriko 静岡県立大学, 食品栄養科学部, 助教 (30440283)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | NHE3 / 消化管 / NaCl吸収 / 輸送体 / 食塩 |
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| Outline of Final Research Achievements |
Transport activity of intestinal Na/H exchanger 3 isoform (NHE3) is sensitive to intracellular pH (pHi). At resting pHi, a large fraction of transporters resides in an inactive state. When the H+ concentration of the cytosol rises, the transporters are converted into an active state. We have previously shown that NHE3 is slowly activated over the course of minutes, implying involvement of a conformational change of NHE3 such as dimerization in heterogenous expression systems. Under physiological conditions, NHE3 is thought to be coupled with other transporters in a concerted manner. To gain insight into the activation mechanism of NHE3, we used the NHE3 specific inhibitor tenapanor, which has a symmetrical structure with two proposed binding sites. Our results suggested that tenapanor may irreversibly bind to NHE3 and recognize the different NHE3 transport modes.
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| Academic Significance and Societal Importance of the Research Achievements |
Na+/ H+交換輸送体(NHE)3はNa+吸収と交換にH+を細胞外に排出している。このためNHE3は、Na+吸収と同時に、細胞内pH調節にも関与する。本研究ではNHE3阻害剤を用いて、NHE3の機能活性をNaCl吸収機能(Cl-輸送体とカップルする)とH+排出機能(H+依存性ペプチド吸収とカップルする)として評価した。NHE3阻害剤は前者を大きく抑制しないが、後者を強く抑制した。これはNHE3とカップルする輸送体によりNHE3阻害剤の作用機構が異なることが理由として考えられた。研究成果は新たな腸管からのNa+吸収抑制機序の発見に繋がる可能性が示唆された。
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Report
(3 results)
Research Products
(4 results)
