Mechanisms for HィイD1+ィエD1 secretion and HィイD1+ィエD1 reabsorption in the distal tubule
| Project/Area Number |
09671172
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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, Dept Nephrol, Instructor, 医学部, 助手 (00285777)
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| Co-Investigator(Kenkyū-buntansha) |
MUTO Shigeaki Jichi Medical School, Dept Nephrol, Assistant Professor, 医学部, 講師 (40190855)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Mesangial cell / NaィイD1+ィエD1-HィイD1+ィエD1 exchange / Hyperosmolality / Intracellular pH / Chloride ion / HCO3共輸送体 / メサンギウム細胞 / NaH交換輸送体 / 高浸透圧 / Cl濃度 / Cl^-濃度 |
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| Research Abstract |
A variety of cell types regulate their volume in anisosmotic media by stimulating NaィイD1+ィエD1-HィイD1+ィエD1 exchange (NHE) activity. However, it is not known whether hyperosmotic stress affects NHE activity in mesangial cells (MC). To examine the effect of hyperosmolality on NHE activity in MCs, we used a pH sensitive dye (BCECF), to measure intracellular pH (pHィイD2iィエD2) in single MC from rat glomeruli. All experiments were performed in C0ィイD22ィエD2/HCOィイD23ィエD2-free HEPES solutions. Exposure of MCs to hyperosmotic HEPES solutions (500 mOsm/kgHィイD22ィエD2O) treated with mannitol caused cell alkalinization. The hyperosmolality-induded cell alkalinization was inhibited by 100 μM EIPA, a specific NHE inhibitor, and was dependent on extracellular NaィイD1+ィエD1. The hyperosmolality shifted the NaィイD1+ィエD1-dependent acid extrution rate vs. pHィイD2iィエD2 by 0.15-0.3 in the alkaline direction. Removal of extracellular ClィイD1"ィエD1 by replacement with gluconate completely abolished the rate of cell alkal
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inization induced by hyperosmolality and inhibited the NaィイD1+ィエD1-dependent acid extrusion rate, whereas under isosmotic conditions, it caused no effect on NaィイD1+ィエD1-dependent pH recovery rate or NaィイD1+ィエD1-dependent acid extrusion rate. The relationship between extracellular ClィイD1"ィエD1 concentrations and the rate of cell alkalinization (dpHィイD1iィエD1/dt) induced by hyperosmolality was sigmoidal: The apparent 50% inhibitory cencentration of extracellular ClィイD1"ィエD1 for the dpHィイD2iィエD2/dt induced by hyperosmolality at pHィイD2iィエD2 of 6.85 was 69.2 mM..The C1ィイD1-ィエD1deoendent cell alkalinization rate under hyperosmotic conditions was partially inhibitetd by pretreatment with NPPB, DIDS and colchicine. When the extracellular C1ィイD1-ィエD1 was replaced with I, Br, SCN, F or gluconate, initial acid extrusion rate induced by hyperosmolality yielded an apparent specificity of Cl>Br>I>SCN>F=gluconate.
We conclude : (a)In MCs, hyperosmolality activates NHE to cause cell alkalinization; (b)The acid extrution rate via NHE is greater under hyperosmotic conditions than under isosmotic conditions at a wide range of pHィイD2iィエD2; (c ) Extracellular C1ィイD1"ィエD1 requires NHE activation induced by hyperosmolality, but does not influence NHE activity under isosmotic condition; (d)The C1ィイD1"ィエD1-dependent NHE activation under hyperosmotic conditions partly occurs via C1ィイD1"ィエD1 channel- and microtubule-dependent process; and (e)Substitution of extracellular C1ィイD1"ィエD1 with different anions modulates NHE activation induced by hyperosmolality. Less
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Report
(4 results)
Research Products
(6 results)
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[Publications] Muto,S., Nemoto,J., Okada,K., Miyata,Y., Kawakami K., Saito,T., and Asano,Y: "Intracellular NaィイD1+ィエD1 directory modulates NaィイD1+ィエD1, KィイD1+ィエD1-ATPase gene expression in normal rat epithelial cells."Kid. Intern. (in press).
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