The effect and regulation mechanism of endothelin and nitric oxide specific in human proximal tubule
| Project/Area Number |
25461241
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Horita Shoko 東京大学, 医学部附属病院, 助教 (20534895)
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| Co-Investigator(Kenkyū-buntansha) |
Suzuki Masashi 東京大学, 医学部附属病院, 助教 (90595662)
Seki Joji 東京大学, 医学部附属病院, 講師 (30206619)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 高血圧 / NO / ET / Na再吸収 / 近位尿細管 / Na輸送 / 尿細管 |
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| Outline of Final Research Achievements |
We found that Angiotensin II (AngII) induces a dose-dependent profound stimulation of human proximal tubule (PT) transport by type 1 AngII receptor (AT1)-dependent phosphorylation of ERK. In PTs of wild-type mice, NO/cGMP/cGKII pathway mediated the inhibitory effect of Ang II, while MEK/ERK pathway mediated the stimulatory effect. Conversely, in human PTs, the NO/cGMP/ERK pathway mediated the stimulatory effect of Ang II. The intracellular Ca2+ did not have any effect on PT transport in mice, but dose-dependently stimulated human PT transport. Endothelin (ET), like AngII, induced very subtle biphasic effect on mice PT, while induced a dose-dependent strong stimulation of human PT transport. These contrasting responses to the NO/cGMP pathway may largely explain the different modes of PT transport regulation by AngII, and the unopposed marked stimulation of PT transport by high intrarenal concentrations of AngII may be an important factor in the pathogenesis of human hypertension.
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] A pure chloride channel mutant of CLC-5 causes Dent’s disease via insufficient V-ATPase activation2016
Author(s)
Nobuhiko Satoh, Hideomi Yamada, Osamu Yamazaki, Masashi Suzuki, Motonobu Nakamura, Atsushi Suzuki, Akira Ashida, Daisuke Yamamoto, Yoshitsugu Kaku, Takashi Sekine, George Seki, Shoko Horita
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Journal Title
Pfluegers Aｒch
Volume: 印刷中
Issue: 7
Pages: 1183-96
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Preserved Na/HCO3 cotransporter sensitivity to insulin may promote hypertension in metabolic syndrome.2015
Author(s)
Nakamura M, Yamazaki O, Shirai A, Horita S, Satoh N, Suzuki M, Hamasaki Y, Noiri E, Kume H, Enomoto Y, Homma Y, Seki G
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Journal Title
Kidney Int.
Volume: 87
Issue: 3
Pages: 535-542
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] 2Cl/H exchange function of CLC-5 is required for the maximal endosome acidification2014
Author(s)
Nobuhiko Sato, Hideomi Yamada, Osamu Yamazaki, Shoko Horita, Masashi Suzuki, Motonobu Nakamura, Yoshitsugu Kaku, Daisuke Yamamoto, Akira Ashida, Takashi Sekine, George Seki
Organizer
American Society of Nephrology Kidney Week 2014
Place of Presentation
Philadelphia, USA
Year and Date
2014-11-14 – 2014-11-16
Related Report
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[Presentation] Loss of 2Cl/H Exchange Function of CLC-5 Causes Dent’s Disease2013
Author(s)
Nobuhiko Sato, Hideomi Yamada, Osamu Yamazaki, Shoko Horita, Masashi Suzuki, Motonobu Nakamura, Yoshitsugu Kaku, Daisuke Yamamoto, Akira Ashida, Takashi Sekine, George Seki.
Organizer
Kidney Week 2013
Place of Presentation
Atlanta, U.S.A.
Related Report
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