Molucular mechanism in the control of water metabolism : integrated study of hypothalamus and kidney

控制水代谢的分子机制：下丘脑和肾脏的综合研究

• 批准号: 11671096
• 负责人: SAITO Toshikazu
• 金额: $ 0.64万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671096/
• 关键词: aquaporin-2; vasopressin; hypothalamus; hyponatremia; 浸透圧刺激; 循環血液量; Fos; アクアポリン2; 水過剰状態; 尿濃縮力; ストレス; グルココルチコイド

Water balance in the body is regulated by the thirst mechanism and vasopressin (AVP) release controlled by the hypothalamus. Antidiuretic action of AVP in the kidney is also regulated by various factors. In the present study, integrated correlation of hypothalamus and kidney in the water homeostasis was examined from the point of molecular aspects. The neural activity of AVP cells in the supraoptic nuclei in the hypothalamus was examined in rats by immuno-staining of c-Fos. Infusion of hypertonic saline to rats intensified its expression and this response was exaggerated by the fall of circulation blood volume after hemorrhage even under the absence of change in its basal activity. This finding indicates the integrated function of AVP cells to both osmotic and volume stimuli. In the rats with hereditary hypothalamic diabetes insipidus, Brattleboro strain, expression of vasopressin dependent water channel, AQP-2, remained low even after vigorous water deprivation. The expression of AQP-2 is intensified in the rats with glucocorticoid deficiency and attenuated under the hyponatremic states resulting in the exaggeration and attenuation of urine concentration ability, respectively. Thus, in the action of AVP in the kidney, the regulation of AQP-2 takes a crucial role in forming a balanced circumstances of water homeostasis in the body.

体内的水分平衡由口渴机制和下丘脑控制的加压素（AVP）释放调节。AVP在肾脏中的抗利尿作用也受到多种因素的调节。本研究从分子水平探讨了下丘脑与肾脏在水稳态中的整体相关性。用c-Fos免疫组织化学染色法观察了大鼠下丘脑视上核AVP细胞的神经活动。输注高渗盐水的大鼠加强其表达，这种反应被夸大了出血后的循环血容量下降，即使在其基础活动的变化的情况下。这一发现表明AVP细胞对渗透压和体积刺激的整合功能。在遗传性下丘脑性尿崩症大鼠中，即使在剧烈缺水后，加压素依赖性水通道AQP-2的表达仍然很低。糖皮质激素缺乏时AQP-2表达增强，低钠状态下AQP-2表达减弱，分别导致尿浓缩能力增强和减弱。因此，在AVP在肾脏中的作用中，AQP-2的调节在形成体内水稳态的平衡环境中起着至关重要的作用。

项目成果

斉藤寿一: "下垂体炎の病態と治療"内分泌・糖尿病科. 11・6. 534-540 (2000)

Juichi Saito：“垂体炎的病理学和治疗”内分泌和糖尿病科11・6（2000）。

Saito Takako: "Lack of vasopressin-independent upregulation of AVP-2 gene expression inhomozygous Battleboro rats"Am.J.Physiol. 277. R427-R433 (1999)

Saito Takako：“在纯合子 Battleboro 大鼠中缺乏不依赖于加压素的 AVP-2 基因表达上调”Am.J.Physiol。

石川 三衛: "水代謝異常症における水チャネルアクアポリン-2の診断応用"臨床病理. 47.5. 402-407 (1999)

Sane Ishikawa：“水通道水通道蛋白-2 在水代谢紊乱中的诊断应用”临床病理学 47.5（1999）。

Saito, T., Higashiyama, M., Fukagawa, A., et al.: "Close correlation of urinary aquaporin-2 with appropriate and inappropriate arginine vasopressin-dependent ・・・・・"J. Clin. Endocrinol. Metab.. 86. 1665-1671 (2001)

Saito, T.、Higashiyama, M.、Fukakawa, A. 等人：“尿水通道蛋白 2 与适当和不适当的精氨酸加压素依赖性的密切相关……”J. Clin Metab.。 1665-1671 (2001)

斉藤寿一: "尿崩症の分子メカニズメ"現代医療. 32・7. 1643-1648 (2000)

斋藤十一：“尿崩症的分子机制”现代医学32・7。