Role of newly discovered endothelin-1(1-31) on renal injury

新发现的内皮素-1(1-31)在肾损伤中的作用

• 批准号: 10670085
• 负责人: TAMAKI Toshiaki
• 金额: $ 2.11万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670085/
• 关键词: Endothelin-1(1-31); Afferent arteriole; Efferent arteriole; Cultured human mesangial cells; intracellular CaィイD12+ィエD1; ERK; Plasma concentration; ET-1; ヒト腎臓組織

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.

1) 合成内皮素 (ET)-1(1-31) 降低微灌注兔肾传入和传出小动脉的管腔直径，呈剂量依赖性。 ET-1(1-31) 诱导的肾小动脉血管收缩不受磷酰胺（一种内皮素转换酶抑制剂）的影响。 ET-1(1-31)通过ETiiD2AiiD2或ETiiD2AiiD2样受体表现出血管活性。2)ET-1(1-31)增加培养的人系膜细胞(HMC)中的细胞内CaiiD12+iiD1。 ET-1(1-31) 的生理活性可能归因于CaィイD12+ィエD1 从细胞内储存的动员，而不是CaィイD12+ィエD1 从细胞外空间流入HMC。3) ET-1(1-31) 导致[ィイD13ィエD1H]-胸苷增加以浓度依赖性方式掺入 HMC。 ET-1(1-31) 本身可能通过内皮素 ETiiD2AiiD2 或 ETiiD2AiiD2 样受体刺激 HMC 增殖。 ET-1(1-31) 引起系膜细胞生长的重要机制可能部分是通过 PKC 依赖性 ERK1/2 激活来解释的。4) 健康年轻志愿者中免疫反应性 ET-1(1-31) 和 ET-1 的血浆浓度分别为 1.70±0.23 pg/mL 和 2.02±0.16 pg/mL。 ET-1(1-31)的血浆浓度水平与健康年轻人中ET-1的血浆浓度水平相同。

项目成果

H.Houchi,: "Endothelin-1 stimlates sodium-dependent Calcium efflux from bovine adrenal chromaffin cells in curture"Br.J.Pharmacol.. 125. 55-60 (1998)

H.Houchi，：“Endothelin-1 刺激培养物中牛肾上腺嗜铬细胞的钠依赖性钙流出”Br.J.Pharmacol.. 125. 55-60 (1998)

Hitoshi Houchi: "Endothelin-1 stimulates sodium-dependent calcium efflux from bovine adrenal chromaffin cells in culture." Br.J.Pharmacol.125. 55-60 (1998)

Hitoshi Houchi：“Endothelin-1 刺激培养物中牛肾上腺嗜铬细胞的钠依赖性钙流出。”

M.Yoshizumi: "Endothelin-1(1-31),a novel vasoactive peptide,increases [Ca^<2+>]i in humen coronary artery smooth muscle cells." Eur.J.Pharmacol.348. 305-309 (1998)

M.Yoshizumi：“Endothelin-1(1-31)，一种新型血管活性肽，可增加人冠状动脉平滑肌细胞中的[Ca^2>]i。”

M.Yoshizumi: "Endothelin-1(1-31),a novel vasoactivc peptide,ircreases[Ca^<2+>]in human coronary artery smooth muscle cells"Eur.J.Pharamacol.. 348. 305-3093 (1998)

M.Yoshizumi：“Endothelin-1(1-31)，一种新型血管活性肽，增加人冠状动脉平滑肌细胞中的[Ca^<2>]”Eur.J.Pharamacol.. 348. 305-3093 (1998)

D.Inui,: "Mechanism of endothelin-1-(1-31)-induced calcium signaling in human coronary artery smooth muscle cells."Am.J.Physiol.. 276. E1067-E1072 (1999)

D.Inui，：“人冠状动脉平滑肌细胞中内皮素-1-(1-31) 诱导的钙信号传导机制。”Am.J.Physiol.. 276. E1067-E1072 (1999)