Regulation of diuresis by 2 types of antidiuretic hormone receptor in chronic renal failure and therapeutic investigation of edema

2种抗利尿激素受体对慢性肾功能衰竭利尿的调节及水肿治疗研究

• 批准号: 13671121
• 负责人: NONOGUCHI Hiroshi
• 金额: $ 2.24万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671121/
• 关键词: antidiuretic hormone; V1a receptor; V2 receptor; aquaporin 2; trafficking; metabolic acidosis; 転写活性; Vla受容体; 慢性腎不全; 集合尿細管; RT-PCR

We first investigated urinary excretion of aquaporin 2 (AQP2) using Western blot analysis. However, AQP2 was not detectable in the urine. We have been still trying to detect urinary excretion of AQP2 by increasing the sensitivity of Western blot analysis. Urinary excretion of AQP2 was also examined in rats with metabolic acidosis. Urinary excretion of AQP2 was significantly decreased in metabolic acidosis. However, the expressions of AQP2 mRNA and protein in outer medullary collecting ducts were increased. Differential centrifugation revealed that AQP2 expression was decreased in membrane-rich fraction but increased in intracellular vesicle-rich fraction. These data suggest that trafficking of AQP2 from intracellular vesicles to apical membrane is inhibited in metabolic acidosis. The precise mechanisms of the disturbance has to be examined further.

我们首先使用Western blot分析研究了尿中水通道蛋白2 （AQP2）的排泄。尿中未检出AQP2。我们仍在尝试通过提高Western blot分析的敏感性来检测尿中AQP2的排泄量。同时检测代谢性酸中毒大鼠尿中AQP2的排泄量。代谢性酸中毒患者尿中AQP2排泄量明显减少。而外髓集管AQP2 mRNA及蛋白表达增加。差速离心显示，AQP2在富膜部位表达降低，而在胞内富囊泡部位表达升高。这些数据表明，代谢性酸中毒中AQP2从细胞内囊泡向顶膜的转运受到抑制。这种扰动的确切机制还有待进一步研究。

项目成果

Nonoguchi H., et al.: "Angiotensin-converting ezgyme inhibitor withdrawal and ACE gene polymorphism"Clin Nephrol.. (in press).

Nonoguchi H.等人：“血管紧张素转换ezgyme抑制剂戒断和ACE基因多态性”Clin Nephrol..（出版中）。

Kikuchi Y, Nonoguchi H, Machida K, Wakamatsu S, Koga H, Tomita K.: "Regulation of the apoptosis-related genes, Bax and Bcl-2, in the early stage of diabetes mellitus"Nephrology. 7. 294-302 (2002)

Kikuchi Y、Nonoguchi H、Machida K、Wakamatsu S、Koga H、Tomita K.：“糖尿病早期阶段凋亡相关基因 Bax 和 Bcl-2 的调节”肾脏病学。

Imanishi, K., et al.: "Type 1A angiotensin II receptor is regulated differently in proximal and distal nephron segments"Hypertens. Res.. (in press).

Imanishi, K. 等人：“1A 型血管紧张素 II 受体在近端和远端肾单位段中受到不同的调节”Hypertens。

Narikiyo T, Kitamura K, Adachi M, Miyoshi T, Iwashita K, Shiraishi N, Nonoguchi H, Chen LM, Chai KX, Chao J, Tomita K.: "Regulation of prostasin by aldosterone in the kidney"J. Clin. Invest. 109. 401-408 (2002)

Narikiyo T，Kitamura K，Adachi M，Miyoshi T，Iwashita K，Shiraishi N，Nonoguchi H，Chen LM，Chai KX，Chao J，Tomita K.：“肾脏中醛固酮对前列腺素的调节”J。

Tashima Y, Kohda Y, Nonoguchi H, Ikebe M, Machida K, Star RA, Tomita K.: "Intranephron localization and regulation of the V1a vasopressin receptor during metabolic acidosis and dehydration in rats"Pflugers Arch. 442. 652-661 (2001)

Tashima Y、Kohda Y、Nonoguchi H、Ikebe M、Machida K、Star RA、Tomita K.：“大鼠代谢性酸中毒和脱水期间 V1a 加压素受体的肾内定位和调节”Pflugers Arch。