The investigation of the mechanisms and therapy of the abnormality in antidiuretic hormone action in patients with chronic renal failure

慢性肾功能衰竭患者抗利尿激素作用异常的机制及治疗探讨

• 批准号: 15590852
• 负责人: NONOGUCHI Hiroshi
• 金额: $ 2.18万
• 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: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590852/
• 关键词: antidiuretic hormone; V1a receptor; V2 receptor; V1a knockout mice; aquaporin 2; metabolic acidosis; trafficking; 細胞内アシドーシス; 尿濃縮; プロモーター; 集合尿細管

We investigated renal function and abnormality in V1a-knockout mice and found that there is no abnormality in urine concentrating ability. Vasopressin-dependent camp generation in V1a receptor-knockout mice was also not different from control mice. Now, we are investigating V1a receptor transgenic mice.We next investigated urinary excretion of aquaporin-2(AQP2) in rats with metabolic acidosis. Although urinary AQP2 excretion was largely decreased, AQP2 mRNA and protein in outer medullary collecting ducts were increased in rats with metabolic acidosis. These data suggest the presence of abnormality in trafficking of AQP2 from intracellular vesicle to the apical membrane in metabolic acidosis. We observed same tendency in rats with potassium depletion. Since intracellular acidosis is known to occur in metabolic acidosis and potassium depletion, intracellular acidosis may have a key role for the decreased trafficking of AQP2 in the collecting ducts. We are now collaborating with Dr, Nielsen in Aarhus University in Denmark and Dr.knepper in National Institutes of health in USA.

我们对V1a敲除小鼠的肾功能和异常进行了检查，发现尿液浓缩能力没有异常。 V1a 受体敲除小鼠中加压素依赖性阵营的产生也与对照小鼠没有不同。现在，我们正在研究V1a受体转基因小鼠。接下来我们研究了代谢性酸中毒大鼠中水通道蛋白2（AQP2）的尿排泄情况。代谢性酸中毒大鼠中，虽然尿液中AQP2排泄量大幅减少，但外髓集合管中AQP2 mRNA和蛋白却增加。这些数据表明，在代谢性酸中毒中，AQP2 从细胞内囊泡到顶膜的运输存在异常。我们在缺钾的大鼠中观察到同样的趋势。由于已知细胞内酸中毒发生在代谢性酸中毒和钾缺乏中，因此细胞内酸中毒可能对集合管中 AQP2 运输减少具有关键作用。我们现在正在与丹麦奥胡斯大学的 Nielsen 博士和美国国立卫生研究院的 knepper 博士合作。

项目成果

Two male siblings with hereditary renal hypouricemia and exercise-induced ARF

• DOI: 10.1053/j.ajkd.2003.08.032
• 发表时间: 2003-12-01
• 期刊: AMERICAN JOURNAL OF KIDNEY DISEASES
• 影响因子: 13.2
• 作者: Tanaka, M;Itoh, K;Tomita, K
• 通讯作者: Tomita, K

Machida K: "Acute regulation of the eoithelial sodium channel gene by vasopressin and hyperosmolality"Hypertens Res. 26・8. 629-634 (2003)

Machida K：“加压素和高渗透压对上皮钠通道基因的急性调节”Hypertens Res 26・8（2003）。

Gene regulation of renal-osmotic stress-induced Na-Cl organic solute cotransporter.

肾渗透应激诱导的 Na-Cl 有机溶质协同转运蛋白的基因调控。

• 发表时间: 2004
• 期刊: Nephron Exp Nephrol 96
• 作者: Tuyen do G;Kitamura K;Adachi M;Miyoshi T;Wakida N;Nagano J;Nonoguchi H;Tomita K.;Tuyen do G.;Baba T
• 通讯作者: Baba T

Angiotensin-converting enzyme inhibitor withdrawal and ACE gene polymorphism.

血管紧张素转换酶抑制剂戒断与ACE基因多态性。

• 发表时间: 2003
• 期刊: Clin Nephrol. 60
• 作者: Nonoguchi H;Kiyama S;Inoue H;Nakayama Y;Inoue T;Kohda Y;Machida K;Tajima A;Kitamura K;Miyoshi T;Shimada H;Shimada H;Tajiri M;Honda Y;Tanaka M;Tomita K.
• 通讯作者: Tomita K.

Baba T: "Gene Regulation of Renal Osmotic Stress-induced Na-Cl Organic Solute Cotransporter (ROSIT)"Nephron Exp Nephrol. (in press).

Baba T：“肾渗透应激诱导的 Na-Cl 有机溶质协同转运蛋白 (ROSIT) 的基因调节”Nephron Exp Nephrol。