Vasopressin and Aquaporin-2 Water Channel in Impaired Water Excretion

水排泄障碍中的加压素和 Aquaporin-2 水通道

• 批准号: 20591083
• 负责人: ISHIKAWA San-e
• 金额: $ 2.58万
• 依托单位: Jichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591083/
• 关键词: バソプレシン; アクアポリン2; 水利尿不全; 浸透圧; プロモーター活性; 転写調節; 低Na血症; 心筋梗塞; 下垂体機能低下症; バゾプレシン; アクアポリンー2; 蛋白発現; 感染症; アクアポリン-2

In the present study we demonstrated the roles of arginine vasopressin (AVP) and aquaporin-2 (AQP2) water channel in impaired water excretion. In the in vitro study the AQP2 promoter assay clarified the presence of tonicity-response element (TonE) in the AQP2 5'-flanking region (-570～-560 bp) as well as cAMP-response element (CRE) for activating AQP2 transcription. An exposure of cells to hypotonic solution diminished the cAMP-activated AQP2 promoter activity. In the in vivo study the expression of AQP2 mRNA and protein were increased in concert with an increase in plasma AVP in the glucocorticoid-deficient rats. The phenomenon was much manifest in the elder rats with glucocorticoid deficiency. The enhanced expressions of AQP2 mRNA and protein were normalized in the rats after glucocorticoid replacement. Varying levels of serum Na were found in the patients with acute infectious diseases. The group of hyponatremia had an elevation of plasma AVP despite of no reduction in circulatory blood volume. The elevated plasma IL-1β could centrally stimulate AVP release, and produce impaired water excretion and hyponatremia. There was 20.9% of the patients with acute myocardial infarction having hyponatremia within 72 hours after the onset. Plasma AVP was significantly increased in the hyponatremic patients compared with that in the normonatremic ones. There was poor short- and long-term prognosis in the patients with hyponatremia.

在本研究中，我们证明了精氨酸加压素（AVP）和水通道蛋白2（AQP 2）的水通道在受损的水排泄的作用。在体外实验中，AQP 2启动子分析证实了AQP 2 5 '侧翼区（-570~-560 bp）存在张力反应元件（TonE）和cAMP反应元件（CRE），它们都能激活AQP 2的转录。暴露于低渗溶液的细胞减少cAMP激活的AQP 2启动子活性。在体内研究中，在糖皮质激素缺乏大鼠中，AQP 2 mRNA和蛋白的表达与血浆AVP的增加一致地增加。这一现象在老年糖皮质激素缺乏大鼠中更为明显。糖皮质激素替代治疗后，AQP 2 mRNA和蛋白表达水平均恢复正常。急性感染性疾病患者血清钠水平不同。低钠血症组血浆AVP水平升高，但循环血容量无明显减少。血浆IL-1β水平升高可中枢性刺激AVP释放，导致水排出障碍和低钠血症。急性心肌梗死患者发病72小时内发生低钠血症者占20.9%。低钠血症患者血浆AVP水平明显高于正常血钠者。低钠血症患者的近期和远期预后均较差。

项目成果

Bilateral Aldosteronoma Associated with Secondary Aldosteronism in a Chronic Hemodialysis Subject

慢性血液透析受试者中与继发性醛固酮增多症相关的双侧醛固酮瘤

• DOI: 10.2169/internalmedicine.49.2808
• 发表时间: 2010
• 期刊: Internal Medicine
• 影响因子: 1.2
• 作者: Ikoma A;Saito T;Murata M;Toyoshima H;Nakamura Y;Kawakami M;Sasano H;Ishikawa SE
• 通讯作者: Ishikawa SE

Pathophysiological role of aquaporin-2 in impaired water excretion.

aquaporin-2 在水排泄受损中的病理生理作用。

• 发表时间: 2008
• 期刊: Progress in Brain Research
• 作者: S. Ishikawa;Tomoyuki Saito;Takako Saito;K. Kasono;H. Funayama
• 通讯作者: H. Funayama

Voltage-dependent metabolic regulation of KV2.1 channels in pancreatic B cells

胰腺 B 细胞 KV2.1 通道的电压依赖性代谢调节

• 发表时间: 2010
• 期刊: Biochem Biophys Res Commun
• 作者: Ikoma A;Saito T;Murata M;Toyoshima H;Nakamura Y;Kawakami M;Sasano H;Ishikawa S;Yoshioka T;Sasaki M;Yoshida M
• 通讯作者: Yoshida M

State-of-art-lecture Arginine vasopressin agonists and antagonists : Development and clinical use. In : Symposium "Vasopressin agonist and antagonist"

最先进的讲座精氨酸加压素激动剂和拮抗剂：开发和临床应用。

• 发表时间: 2010
• 作者: Kitagawa H.;Fujiki R.;Yoshimura K.;Oya H.;Kato S.;Nakajima Y;石川三衛
• 通讯作者: 石川三衛

ミートザスペシャリスト講演「水・Na代謝異常と間脳下垂体」

专家讲座：“水/钠代谢异常与间脑垂体”

• 发表时间: 2009
• 作者: Satoh T;Ishizuka T;Yoshino S;Tomaru T;Nakajima Y;Shibusawa N;Hashimoto K;Yamada M;Mori M;石川三衛
• 通讯作者: 石川三衛