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.

• 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
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• 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 / V1a受容体ノックアウトマウス / 抗体利尿ホルモン / V2受容体 / V1a受容体 / 介在細胞 / 腎尿細管性アシドーシス / プロモーター活性 / 集合尿細管 / 尿濃縮 / LLC-PK1細胞

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
  • NAID: 10024831162
• [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
  • NAID: 10026122512
• [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: 360-360
• [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
• [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: 364-364
• [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] A case with acute renal failure and subsequent nephrotic syndrome. (2009)
  • Author(s): Nonoguchi H, et al.
  • Journal Title: Renal Fail. 31 Pages: 162-166
  • Peer Reviewed
• [Journal Article] Different Mechanisms for the Progression of CKD with ACE Gene Polymorphisms. (2009)
  • Author(s): Nakayama Y, Nonoguchi H, et al.
  • Journal Title: Nephron Clin Pract. 111
  • Peer Reviewed
• [Journal Article] Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts. (2009)
  • Author(s): Mouri T, Nonoguchi H, et al.
  • Journal Title: Hypertens Res 32 Pages: 358-363
  • NAID: 10026122512
  • Peer Reviewed
• [Journal Article] Vasopressin and Hyperosmolality Regulate NKCCl Expression in Rat OMCD (2009)
  • Author(s): Wakamatsu S, Nonoguchi H, et al.
  • Journal Title: Hypertens Res 32(In press)
  • Peer Reviewed
• [Journal Article] Enhanced kidney, gallbladder and colon on delayed CT (2009)
  • Author(s): Munemoto M, Nonoguchi H, et al.
  • Journal Title: Nephrology 14 Pages: 360-360
  • Peer Reviewed
• [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
• [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
• [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] Functional and immunochemical characterization of a novel organic anion transporter Oat8 (Slc22a9)in rat renal collecting duct. (2008)
  • Author(s): Yokoyama H, Nonoguchi H, et al.
  • Journal Title: Cell Physiol Biochem 21 Pages: 269-278
  • Peer Reviewed
• [Journal Article] Vasopressin regulates the renin-angiotensin-aldosterone system via vlareceptors in macula densa cells. (2008)
  • Author(s): Izumi Y, Nonoguchi H, et al.
  • Journal Title: Am J Physiol Renal Physiol 295
  • Peer Reviewed
• [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, Nonoguchi H, et al.
  • Journal Title: Clin Nephrol 69 Pages: 402-407
  • Peer Reviewed
• [Journal Article] Regulation of V2R transcription by hypertonicity and V1aR-V2R signal interaction. (2008)
  • Author(s): Izumi Y, Nonoguchi H, et al.
  • Journal Title: Am J Physiol Renal Physiol. 295
  • Peer Reviewed
• [Journal Article] Renal outcomes in the ONTARGET study. (2008)
  • Author(s): Nonoguchi H, Nakanishi T, et al.
  • Journal Title: Lancet 372 Pages: 2019-2020
  • Peer Reviewed
• [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: 1517-1517
• [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
• [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
• [Journal Article] Downregulation of the V2 vasopressin receptor in dehydration:mechanisms and role of renal prostaglandin synthesis. (2007)
  • Author(s): Machida K, et. al.
  • Journal Title: Am J Physiol Renal Physiol 292
  • Peer Reviewed
• [Journal Article] Downregulation of vasopressin V2 receptor promoter activityvia V1a receptor pathway. (2007)
  • Author(s): Izumi Y, et. al.
  • Journal Title: Am J Physiol Renal Physiol 292
  • Peer Reviewed
• [Journal Article] Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced acute renal failure. (2007)
  • Author(s): Matsuzaki N, et. al.
  • Journal Title: Kidney Int 71 Pages: 539-47
  • Peer Reviewed
• [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, et. al.
  • Journal Title: Ther Apher Dial. 11 Pages: 42-48
  • Peer Reviewed
• [Journal Article] Target haemoglobin concentrations in chronic kidney disease. (2007)
  • Author(s): Nonoguchi H, et. al.
  • Journal Title: Lancet 369 Pages: 1017-1017
  • Peer Reviewed
• [Journal Article] Low-responders to angiotensin II receptor blockers and genetic polymorphism in angiotensin-converting enzyme. (2007)
  • Author(s): Nonoguchi H, et. al.
  • Journal Title: Clin Nephrol 68 Pages: 209-15
  • Peer Reviewed
• [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. (2007)
  • Author(s): Matsuzaki N, et. al.
  • Journal Title: Drug Metab Dispos. 36 Pages: 649-54
  • Peer Reviewed
• [Journal Article] The MAXIMA trial. (2007)
  • Author(s): Nonoguchi H, et. al.
  • Journal Title: Lancet 371 Pages: 299-300
  • Peer Reviewed
• [Journal Article] Long-term plasma levels and dose modulation of alacepril in patients with chronic renal failure. (2007)
  • Author(s): Nonoguchi H, et. al.
  • Journal Title: Hypertens Res 31 Pages: 29-36
  • NAID: 10021260933
  • Peer Reviewed
• [Presentation] Vasopressin V1a receptor deficient causes a new type of nephrogenic diabetes insipidus. (2008)
  • Author(s): Izumi Y, Nonoguchi, et al.
  • Organizer: 米国腎臓学会
  • Place of Presentation: Philadelphia
  • Year and Date: 2008-11-08
• [Presentation] Vasopessin regulates the rein-angiotensin-aldosterone system via V1a receptors in macula densa cells. (2008)
  • Author(s): Aoyagi T, Nonoguchi, et al.
  • Organizer: 米国腎臓学会
  • Place of Presentation: Philadelphia
  • Year and Date: 2008-11-08
• [Presentation] Acidosis stimulates the vasopressin V2 receptor promoter activity and enhances the suppression of V2R expression by V1a receptor stimulation. (2008)
  • Author(s): Memetimin H, Nonoguchi, et al.
  • Organizer: 米国腎臓学会
  • Place of Presentation: Philadelphia
  • Year and Date: 2008-11-08
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Regulation of vasopressin V2 receptor promoter activity by hypertonicity and V1a receptor pathway. (2007)
  • Author(s): Izumi Y
  • Organizer: 米国腎臓学会
  • Place of Presentation: San Francisco
  • Year and Date: 2007-11-02