The investigation of the mechanisms and the rapy of renal edema from the acpect of cell porality.

从细胞多孔性角度探讨肾水肿发生机制及治疗方法。

• 批准号: 06671133
• 负责人: NONOGUCHI Hiroshi
• 金额: $ 1.34万
• 依托单位: Kumamoto University (1995)Tokyo Medical and Dental University (1994)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671133/
• 关键词: antidiuretic hormone; V_2 receptor; V_1a receptor; edema; inner medullary collecting duct; chronic renal failure; vasopressin (AVP); Vlaレセプター; V2(AOP)レセプター; 細胞極性

We investigated immunohistochemical localization of V2 vasopressin (antidiuretic hormone) receptor along the nephron using a specific polyclonal antibody. V2 receptor was present in some of thick ascending limbs and all of pricipal and inner medullary collecting duct (IMCD) cells. Not only basolateral but also luminal membrane was stained by the antibody in collecting ducts, especially in terminal IMCD.Therefore, to learn the functional role of luminal V2 receptor in terminal IMCD,we investigated the luminal effects of vasopressin on osmotic water permeability (Pf), urea permeability (Pu), and cAMP accumulation using isolated perfused rat terminal IMCD.Luminal vasopressin caused a small increase in cAMP accumulation, Pf and Pu in the absence of bath vasopressin. In contrast, luminal vasopressin inhibited Pf and Pu by 30-65% in the presence of bath vasopressin by decreasing cAMP accumulation via V1a or oxytocin receptors and by an unknown mechanism via V2 receptors in the luminal membrane of terminal IMCD.Therefore, luminal vasopressin acts as an diuretic hormone rather than antidiuretic hormone in terminal IMCD.

我们用一种特定的多克隆抗体研究了V2加压素(抗利尿激素)受体沿肾单位的免疫组织化学定位。V2受体存在于部分粗大的升支和所有的主、内髓集合管细胞。因此，为了了解腔V2受体在终末IMCD中的作用，我们观察了血管加压素对终末IMCD渗透水通透性(Pf)、尿素通透性(Pu)和cAMP积聚的影响。相反，腔内加压素可通过V1a或催产素受体和未知的V2受体抑制终末期IMCD的cAMP积聚，从而抑制Pf和Pu达30-65%。因此，在终末期IMCD中，腔内加压素作为利尿激素而不是抗利尿激素。

项目成果

T.Shiigai,H.Nonoguchi,K.Tomita: "Dietary protein restriction and blood-pressue control in chron:c renal inaufficieney" N.Engl.J.Med.331. 405-406 (1994)

T.Shiigai、H.Nonoguchi、K.Tomita：“慢性肾功能不全中的饮食蛋白质限制和血压控制”N.Engl.J.Med.331。

Y.Terada,et al.: "Presence and requlation of RAF-1-K(Kinase). MAPK-K,MAP-K,and S6-K in rat nephon segments." J.Am.Soc.Nephrol.6. 1566-1577 (1995)

Y.Terada 等人：“大鼠肾段中 RAF-1-K（激酶）、MAPK-K、MAP-K 和 S6-K 的存在和调节。”

Y.Terada,et al.: "Sequential activation of Raf-1 kinase,mitogen-activots protein (MAP) kinase kinase,MAP kinase,and S6 kinaseby hyperosmolalily in renol cells" J.Biol.Chem.268. 31296-31301 (1994)

Y.Terada 等人：“Raf-1 激酶、丝裂原激活蛋白 (MAP) 激酶激酶、MAP 激酶和 S6 激酶在肾醇细胞中通过高渗透压的顺序激活”J.Biol.Chem.268。

M.Yoshida: "Three cases of malignant hypertension: the roles of endothelin-1 and the renin-angiotensin-aldosterone system." Clin Nephrol.42. 295-299 (1994)

M.Yoshida：“三例恶性高血压：内皮素-1 和肾素-血管紧张素-醛固酮系统的作用。”

A.Owada,: "Endothelin(ET)-3 stimulates cyclic guanosine 3,5-monophosphate production via ET_B receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells." J. Clin. Invest.93. 556-563 (1994)

A.Owada：“内皮素 (ET)-3 通过 ET_B 受体在离体大鼠肾小球和培养的大鼠肾小球膜细胞中产生一氧化氮，从而刺激环鸟苷 3,5-单磷酸的产生。”