| Project/Area Number |
15590857
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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 |
MIYATA Yukio JICHI MEDICAL SCHOOL, School of Medicine, Lecturer, 医学部, 講師 (00285777)
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| Co-Investigator(Kenkyū-buntansha) |
MUTO Shigeaki JICHI MEDICAL SCHOOL, School of Medicine, assistant professor, 医学部, 助教授 (40190855)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | aldosterone / Na / H exchanger / eplerenone / P-糖蛋白質 / Protein kinase C / PI-3 kinase / Tyrosine kinase / 血管平滑筋細胞 / 非ゲノム作用 / ゲノム作用 |
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| Research Abstract |
Objectives
We have reported that exposure of vascular smooth muscle cells (VSMCs) to aldosterone for 3 and 24 h activated Na^+/H^+ exchange (NHE) via nongenomic and genomic mechanisms, respectively. The present study determined whether aldosterone-induced nongenomic and genomic NHE activation depends on the number of transporters, the turnover rate of a single transporter, and/or the change in intracellular pH (pH_i) sensitivity of the transporter, and whether aldosterone-induced NHE activation is inhibited by the selective mineralocorticoid receptor (MR) antagonist (eplerenone).
Methods
Using a fluorescent dye, we assessed NHE activity by Na^+ dependent acid excursion rates (J_H) after an acid load in the absence of CO_2/HCO_3^- in VSMCs treated with aldosterone
Results
Treatment with aldosterone for 3 and 24h increased J_H at the wide pH_i range, and shifted the J_H versus pH_i in the alkaline direction. Without affecting the apparent Km for external Na^+, the Vmax increased in VSMCs treated with aldosterone for 3 and 24h. Both eplerenone and spironolactone inhibited only aldosterone-induced genomic NHE activation, but the IC_<50> of eplerenone was smaller than that of spironolactone.
Conclusion
We determined that : (1) both nongenomic and genomic stimulatory effects of aldosterone on NHE activity in VSMCs occur by the increase in the number of NHE ; (2) only the aldosterone-induced genomic NHE activation occurs via MR ; and (3) both eplerenone and spironolactone inhibit the aldosterone-induced genomic NHE activation, but eplerenone is more effective than spironolactone, based on the IC_<50> value in VSMCs
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