The role of vasopressin V1a receptor in diabetic nephropathy and the invention of new therapy.

加压素V1a受体在糖尿病肾病中的作用及新疗法的发明。

• 批准号: 21591064
• 负责人: NONOGUCHI Hiroshi
• 金额: $ 2.91万
• 依托单位: Hyogo 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: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591064/
• 关键词: 水・電解質代謝学; 抗利尿ホルモン; レニン・アンジオテンシン・アルドステロン系; ミネラルコルチコイド受容体; 細胞質核内輸送; V1a受容体; アルドステロン; 腎尿細管性アシドーシス; ミネラロコルチコイド受容体; 細胞質・核輸送; 核内受容体; 介在細胞; V2受容体; ノックダウン; 抗体利尿ホルモン; ノックアウトマウス; トランスジェニックラット; H-ATPase

We reported that vasopressin V1a receptor deficient mice show type 4 renal tubular acidosis, which is characterized by reduced renal function, metabolic acidosis and hyperkalemia. Since the colleting ducts are the main cite of acid secretion by the kidney, we established a new cell line of the intercalated cells(IN-IC cells) from SV40 large T antigen Tg rats. Using these cells, we also found that vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor by aldosterone in the intercalated cells. In conclusion, vasopressin V1a receptor is essential for acid-base regulation by aldosterone in intercalated cells. These data suggest the possibility of clinical use of vasopressin V1a receptor antagonist as an aldosterone antagonist.

我们报道了加压素V1A受体缺乏的小鼠显示4型肾小管酸中毒，其特征是肾功能降低，代谢性酸中毒和高钾血症。由于夹夹管是肾脏对酸分泌的主要援引，因此我们从SV40大的T抗原TG大鼠中建立了一个新的插入细胞（IN-IC细胞）的细胞系。使用这些细胞，我们还发现，加压素V1A受体是醛固酮在插层细胞中通过醛固酮在矿物皮质激素受体中的核质转运所必需的。总之，加压素V1A受体对于醛固酮在插入细胞中的酸碱调节至关重要。这些数据表明，加压素V1A受体拮抗剂作为醛固酮拮抗剂的临床使用可能性。

项目成果

Mechanisms of Type 4(hyperkalemic) Renal Tubular Acidosis

4型（高钾血症）肾小管性酸中毒的机制

• 发表时间: 2010
• 作者: Hori K;Nagai T;Izumi Y;Nakayama Y;Hasuike Y;Nanami M;Yasuoka Y;Otaki Y;Tanoue A;Kawahara K;Tomita K;Nakanishi T;Nonoguchi H.
• 通讯作者: Nonoguchi H.

Interaction of aldosterone and vasopressin in the intercalated cells of the collecting ducts

醛固酮和加压素在集合管闰细胞中的相互作用

• 发表时间: 2010
• 作者: Kahori Hori;et al.
• 通讯作者: et al.

Acid decreased the expression of Ca-sensing receptor in type-B of mouse kidney collecting duct intercalated cells

酸降低小鼠肾集合管嵌入细胞B型Ca2+敏感受体的表达

• 发表时间: 2011
• 作者: Yasuoka Y;Sato Y;Izumi Y;Nonoguchi H;Kawahara K
• 通讯作者: Kawahara K

Aldosterone Requires Vasopressin V1a Receptors on Intercalated Cells to Mediate Acid-Base Homeostasis

• DOI: 10.1681/asn.2010050468
• 发表时间: 2011-04-01
• 期刊: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
• 影响因子: 13.6
• 作者: Izumi, Yuichiro;Hori, Kahori;Nonoguchi, Hiroshi
• 通讯作者: Nonoguchi, Hiroshi

Vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor

• DOI: 10.1152/ajprenal.00052.2012
• 发表时间: 2012-10-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
• 影响因子: 4.2
• 作者: Hori, Kahori;Nagai, Takanori;Nonoguchi, Hiroshi
• 通讯作者: Nonoguchi, Hiroshi