The investigation of the role of interaction of two types of antidiuretic hormone receptors for diuresis and the invention of the new therapy for renal edema.

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Hyogo College of Medicine (2008); Kumamoto University (2007)
• Principal Investigator: NONOGUCHI Hiroshi Hyogo College of Medicine, 医学部, 准教授 (30218341)
• Co-Investigator(Kenkyū-buntansha): TOMITA Kimio 熊本大学, 医学薬学研究部, 教授 (40114772)
• Project Period (FY): 2007 – 2008
• Keywords: 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

Research Abstract

抗利尿ホルモンの利尿作用には、V2受容体が関与し、V1a受容体は、意味のない受容体と考えられてきたが、私達は、V1a 受容体がV2受容体を介した抗利尿作用を抑制するだけでなく、レニン・アンジオテンシン・アルドステロン(RAS)系の入り口としてmacula densa 細胞に存在し、集合尿細管では、介在細胞においてアルドステロン作用を制御することで、酸塩基平衡の調節をも司っていることを明らかにした。

Research Products

• [Journal Article] Vasopressin and hyperosmolality regulate NKCC1 expression in rat OMCD. (2009)
  • Author(s): Wakamatsu S, Nonoguchi H, Ikebe M, Machida K, Izumi Y, Memetimin H, Nakayama Y, Nakanishi T, Kohda Y, Tomita K.
  • Journal Title: Hypertens Res 32 Pages: 481-7
• [Journal Article] Acute and chronic metabolic acidosis interfere with aquaporin-2 translocation in the rat kidney collecting ducts. (2009)
  • Author(s): Mouri T, Inoue T, Nonoguchi H, Nakayama Y, Miyazaki H, Matsuzaki T, Saito H, Nakanishi T, Kohda Y, Tomita K.
  • Journal Title: Hypertens Res 32 Pages: 358-63
• [Journal Article] Enhanced kidney, gallbladder and colon on delayed CT. (2009)
  • Author(s): Munemoto M, Kawai K, Yamamoto S, Nonoguchi H, Nakanishi T.
  • Journal Title: Nephrology 14 Pages: 360
• [Journal Article] Different mechanisms for the progression of CKD with ACE gene polymorphisms. (2009)
  • Author(s): Nakayama Y, Nonoguchi H, Kohda Y, Inoue H, Memetimin H, Izumi Y, Tomita K.
  • Journal Title: Nephron Clin Pract 111 Pages: c240-6
• [Journal Article] Minerva :calcification of the intestine (2009)
  • Author(s): Munemoto M, Yahiro M, Kawanishi H, Nonoguchi H, Nakanishi T.
  • Journal Title: BMJ 338 Pages: 364
• [Journal Article] A case with acute renal failure and subsequent nephrotic syndrome. (2009)
  • Author(s): Nonoguchi H, Kohda Y, Nakanishi T, Fukutomi R, Nakayama Y, Naruse M, Kitamura K, , Inoue T, Nakanishi T, Tomita K.
  • Journal Title: Renal Fail 31 Pages: 162-6
• [Journal Article] Renal outcomes in the ONTARGET study. (2008)
  • Author(s): Nonoguchi H, Nanami M, Hasuike Y, Kuragano T, Nakanishi T.
  • Journal Title: Lancet 372(9655) Pages: 2019-20
• [Journal Article] Regulation of V2R transcription by hypertonicity and V1aR-V2R signal interaction. (2008)
  • Author(s): Izumi Y, Nakayama Y, Memetimin H, Inoue T, Kohda Y, Nonoguchi H, Tomita K.
  • Journal Title: Am J Physiol Renal Physiol. 295 Pages: F1170-6
• [Journal Article] Long-term observation of renal function on combination therapy with prostaglandin and angiotensin-converting enzyme inhibitor for chronic kidney disease. (2008)
  • Author(s): Nakayama Y, Inoue T, Kohda Y, Inoue H, Izumi Y, Tomita K, Nonoguchi H.
  • Journal Title: Clin Nephrol. 69 Pages: 402-7
• [Journal Article] Vasopressin regulates the renin-angiotensin-aldosterone system via V1a receptors in macula densa cells. (2008)
  • Author(s): Aoyagi T, Izumi Y, Hiroyama M, Matsuzaki T, Yasuoka Y, Sanbe A, Miyazaki H, Fujiwara Y, Nakayama Y, Kohda Y, Yamauchi J, Inoue T, Kawahara K, Saito H, Tomita K, Nonoguchi H, Tanoue A.
  • Journal Title: Am J Physiol Renal Physiol. 295 Pages: F100-7
• [Journal Article] Functional and immunochemical characterization of a novel organic anion transporter Oat8 (Slc22a9) in rat renal collecting duct. (2008)
  • Author(s): Yokoyama H, Anzai N, Ljubojevic M, Ohtsu N, Sakata T, Miyazaki H, Nonoguchi H, Islam R, Onozato M, Tojo A, Tomita K, Kanai Y, Igarashi T, Sabolic I, Endou H.
  • Journal Title: Cell Physiol Biochem. 21 Pages: 269-78
• [Journal Article] Altered pharmacokinetics of cationic drugs caused by down-regulation of renal rat organic cation transporter 2 (Slc22a2) and rat multidrug and toxin extrusion 1 (Slc47a1) in ischemia/reperfusion-induced acute kidney injury. (2008)
  • Author(s): Matsuzaki T, Morisaki T, Sugimoto W, Yokoo K, Sato D, Nonoguchi H, Tomita K, Terada T, Inui K, Hamada A, Saito H.
  • Journal Title: Drug Metab Dispos. 36 Pages: 649-54
• [Journal Article] Low-responders to angiotensin II receptor blockers and genetic polymorphism in angiotensin-converting enzyme. (2007)
  • Author(s): Nonoguchi H, Nakayama Y, Shiigai T, Inoue T, Inoue H, Kohda Y, Honda Y, Tomita K
  • Journal Title: Clin Nephrol. 68 Pages: 209-15
• [Journal Article] Target haemoglobin concentrations in chronic kidney disease. (2007)
  • Author(s): Nonoguchi H, Nakayama Y, Inoue T, Kohda Y, Tomita K.
  • Journal Title: Lancet. 369(9572) Pages: 1517
• [Journal Article] A novel method for dry weight assessment in hemodialysis patients: utilization of inferior vena cava flat ratio to correct for individual variations in vessel diameter. (2007)
  • Author(s): Naruse M, Sakaguchi S, Nakayama Y, Nonoguchi H, Tomita K.
  • Journal Title: Ther Apher Dial. 11 Pages: 42-8
• [Journal Article] Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced acute renal failure. (2007)
  • Author(s): Matsuzaki T, Watanabe H, Yoshitome K, Morisaki T, Hamada A, Nonoguchi H, Kohda Y, Tomita K, Inui K, Saito H.
  • Journal Title: Kidney Int. 71 Pages: 539-47
• [Journal Article] Downregulation of vasopressin V2 receptor promoter activity via V1a receptor pathway. (2007)
  • Author(s): Izumi Y, Nakayama Y, Mori T, Miyazaki H, Inoue H, Kohda Y, Inoue T, Nonoguchi H, Tomita K.
  • Journal Title: Am J Physiol Renal Physiol. 229 Pages: F1418-26
• [Journal Article] Downregulation of the V2 vasopressin receptor in dehydration: mechanisms and role of renal prostaglandin synthesis. (2007)
  • Author(s): Machida K, Wakamatsu S, Izumi Y, Yosifovska T, Matsuzaki T, Nakayama Y, Kohda Y, Inoue T, Saito H, Tomita K, Nonoguchi H.
  • Journal Title: Am J Physiol Renal Physiol. 292 Pages: F1274-82
• [Presentation] Vasopressin V1a receptor deficient causes a new type of nephrogenic diabetes insipidus (2008)
  • Author(s): Izumi Y, Aoyagi T, Hiroyama M, Matsuzaki T, Yasuoka Y, Sanbe A, Miyazaki H, Fujiwara Y, Nakayama Y, Kohda Y, Yamauchi J, Inoue T, Kawahara K, Saito H, Tomita K, Nonoguchi H, Tanoue A
  • Organizer: 51^<st> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Vasopressin V1a receptor deficient causes a new type of nephrogenic diabetes insipidus 51st Annual Meeting of the American Society of Nephrology
  • Year and Date: 20081106-09
• [Presentation] Acidosis stimulates vasopressin V2 receptor promoter activity and enhances the down-regulation induced by V1a receptor stimulation. (2008)
  • Author(s): Memetimin H, Izum Y, Nakayama Y, Kohda Y, Inoue H, Nonoguchi H, Tomita K
  • Organizer: 51^<st> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia
  • Year and Date: 20081106-09
• [Presentation] Renoprotection by inhibition of GSK3 in streptozotocin-induced diabetic nephropathy ; the new approach for reduction of proteinuria through TGF-1 pathway. (2008)
  • Author(s): Nakayama Y, Memetimin H, Izumi Y, Kohda Y, Inoue H, Nonoguchi H, Tomita K.
  • Organizer: 51^<st> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia
  • Year and Date: 20081106-09
• [Presentation] Effects of Citrate and Plasma pH on ALA-stimulated Iron Release from Human Ferritin in vitro. (2008)
  • Author(s): Hasuike Y, Nonoguchi H, Hata R, Nanami M, Kuragano T, Ito K, Kida A, Furuta M, Kitamura R, Hori K, Otaki Y, Nakanishi T
  • Organizer: 51^<st> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia
  • Year and Date: 20081106-09
• [Presentation] 浸透圧刺激ならびにV1a受容体刺激によるバゾプレッシンV2受容体プロモーター活性の調節機構 (2008)
  • Author(s): Memetimin Hasiyet, 泉裕一郎、中山裕史、江田幸政、井上武明、野々口博史、冨田公夫
  • Organizer: 日本腎臓学会学術総会第51回
  • Place of Presentation: 福岡
  • Year and Date: 20080530-0601
• [Presentation] 腎マクラデンサ細胞内バゾプレッシンV1a受容体を介したレニン-アンジオテンシン-アルドステロン系の調節 (2008)
  • Author(s): 泉裕一郎、青柳利紀、廣山眞巳、松崎尊信、安岡有紀子、三部篤、宮崎博喜、藤原葉子、中山裕史、江田幸政、山内淳司、井上武明、河原克雅、齋藤秀之、冨田公夫、野々口博史、田上昭人
  • Organizer: 第51回日本腎臓学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 20080530-0601