1999 Fiscal Year Final Research Report Summary
Role of newly discovered endothelin-1(1-31) on renal injury
| Project/Area Number |
10670085
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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 |
General pharmacology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TAMAKI Toshiaki University of Tokushima, School of Medicine, Department of Pharmacology, Professor, 医学部, 教授 (80179879)
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| Co-Investigator(Kenkyū-buntansha) |
YOSIZUMI Masanori University of Tokushima, School of Medicine, Department of Pharmacology, Associate professor, 医学部, 助手 (60294667)
KIDO Hiroshi University of Tokushima, School of Medicine, Department of Pharmacology, Professor, 分子酵素学研究センター, 教授 (50144978)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Endothelin-1(1-31) / Afferent arteriole / Efferent arteriole / Cultured human mesangial cells / intracellular CaィイD12+ィエD1 / ERK / Plasma concentration |
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| Research Abstract |
1) Synthetic endothelin (ET)-1(1-31) decreased the lumen diameter of microperfused rabbit renal afferent and efferent arterioles, dose-dependently. ET-1(1-31)-induced renal arteriolar vasoconstriction was not influenced by phosphoramidon, an endothelin converting enzyme inhibitor. ET-1(1-31) exhibited vasoactive properties through ETィイD2AィエD2 or ETィイD2AィエD2-like receptors.
2) ET-1(1-31) increased intracellular CaィイD12+ィエD1 in cultured human mesangial cell(HMC). The physiological activity of ET-1(1-31) may be attributable to CaィイD12+ィエD1 mobilization from intracellular stores rater than influx of CaィイD12+ィエD1 from extracellular space in HMC.
3) ET-1(1-31) caused an increase in [ィイD13ィエD1H]-thymidine incorporation into the HMCs in a concentration-dependent manner. ET-1(1-31) itself stimulates HMC proliferation probably through endothelin ETィイD2AィエD2 or ETィイD2AィエD2-like receptors. The underlining mechanism of mesangial cell growth by ET-1(1-31) may be explained in part by PKC-dependent ERK1/2 activation.
4) Plasma concentrations of immunoreactive ET-1(1-31) and ET-1 in healthy young volunteers were 1.70±0.23 pg/mL and 2.02±0.16 pg/mL, respectively. The plasma concentration level of ET-1(1-31) was equal to that of ET-1 in healthy young humans.
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