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Elucidation of the mechanism of essential hypertension making a transgenic mice made by putative kallikrein binding protein

Research Project

Project/Area Number 05557054
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Kidney internal medicine
Research InstitutionKumamoto University (1995)
Tokyo Medical and Dental University (1993-1994)

Principal Investigator

TOMITA Kimio  Kumamoto University, Internal Medicine, Professor, 医学部, 教授 (40114772)

Co-Investigator(Kenkyū-buntansha) INAGAKI O  Yamanouchi Pharmaceutical Comp., Tsukuba Res.Institute, Researcher, 筑波研究所, 研究員
TAKENAKA T  Yamanouchi Pharmaceutical Comp., Tsukuba Res.Institute, Head, 筑波研究所, 所長
TERADA Yoshio  Tokyo Med.& Dent University, Internal Medicine, Assistant Professor, 医学部, 助手 (30251531)
NONOGUCHI Hiroshi  Kumamoto University, Internal Medicine, Associate Professor, 医学部・附属病院, 講師 (30218341)
MARUMO Fumiaki  Tokyo Med.& Dent University, Internal Medicine, Professor, 医学部, 教授 (00050443)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥7,000,000 (Direct Cost: ¥7,000,000)
KeywordsTransgenic mice / Kallikrein / Kidney / Na / Hypertension / Nitric oxide / Glomerulus / トランスジェニックスマウス / 降圧薬 / プロテアーゼ / 尿細管 / キニン / カリクレイン抑制たんぱく / クローニング
Research Abstract

Kallikrein is a key enzyme in the processing of kininogen to release kinins, which exert diuretic and natriuretic actions. The regulation of kallikrein activities is poorly understood. Recently, Chao et al have identified a tissue specific kallikrein-binding protein that inhibits kallikrein activity, in human and rat. The gene coding for kallikrein-binding protein of rat and mouse has been subsequently cloned. It is well known that the renal kallikrein-kinin system is depressed in essential hypertension. The presence of kallikrein-binding protein in the kidney has been suggested by Western blot and Northern blot analysis. We used reverse-transcription and polymerase chain reaction to detect the precise localization of kallikrein-binding protein along the nephron using the microdissection method. In SD rats, the most abundant signals were found in inner medullary collecting duct, with small amount in outer medullary collecting duct, proximal convoluted tubule, and glomerulus. Similar distribution was found in WKY,however, in SHR,only a small amount was detected in inner medullary collecting duct. The presence of kallikrein-binding protein in terminal segment of the nephron suggests the importance of this protein in the regulation of body fluid and probably blood pressure. To explore the role of this protein in the mechanism of essential hypertension, we further tried to make transgenic mice to over-express the kallikrein-binding protein. Now we are processing the isolation of full length gene and express it to mice.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Y.Terada,: "Different localization and regulation of two types of vasopressin receptor messenger RNA in microdissected rat nephron segments using reverse transcription polymerase chain reaction." J. Clin. Invest.92. 2339-2345 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Terada,: "Sequential activation of raf-1 kinase, MAP kinase kinase, MAP kinase, and S6 kinase by hyperosmolality in renal cells." J. Biol. Chem.269. 31296-31301 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Yang,: "Distribution of kallikrein-binding protein mRNA in kidneys and difference between SHR and WKY rats." Am. J. Physiol.267. F325-F330 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Terada,: "Sequential activation of MAP kinase cascade by angiotensin II in opossum kidney cells." Kidney Int.48. 1801-1809 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Nonoguchi,: "Immunohistochemical localization of V2 vasopressin receptor along the nephron and functional role of luminal V2 receptor in terminal inner medullary collecting ducts." J. Clin. Invest.96. 1768-1778 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Terada, K.Tomita, H.Nonoguchi, T.Yang, F.Marumo: "Different localization and regulation of two types of vasopressin receptor messenger RNA in microdissected rat nephron segments using reverse transcription polymerase chain reaction." J.Clin.Invest.92. 2339-2345 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Owada, K.Tomita, H.Nonoguchi, Y.Terada, H.Sakamoto, and F.Marumo: "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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Terada, Kimio Tomita, Miwako Homma, Hiroshi Nonoguchi, Tiaxin Yang, Takehisa Yamada, Yasuhito Yuasa, Edwin G.Krebs, Sei Sasaki and Fumiaki Marumo: "Sequential activation of raf-1 kinase, MAP kinase kinase, MAP kinase, and S6 kinase by hyperosmolality in renal cells." J.Biol.Chem.269. 31296-31301 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Yang, Y.Terada, H.Nonoguchi, M.Tsujino, K.Tomita, F.Marumo: "Distribution of kallikrein-binding protein mRNA in kidneys and difference between SHR and WKY rats." Am.J.Physiol.267. F325-F330 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Terada, Kimio Tomita, Miwako Homma, Hiroshi Nonoguchi, Tiaxin Yang, Takehisa Yamada, Yasuhito Yuasa, Edwin G.Krebs, and Fumiaki Marumo: "Sequential activation of MAP kinase cascade by angiotensin II in opossum kidney cells." Kidney Int.48. 1801-1809 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Nonoguchi, A.Owada, N.Kobayashi, M.Takayama, Y.Terada, J.Koike, K.Ujiie, F.Marumo, T.Sakai, K.Tomita: "Immunohistochemical localization of V2 vasopressin receptor along the nephron and functional role of luminal V2 receptor in terminal inner medullary collecting ducts." J.Clin.Invest.96. 1768-1778 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y Terada,K Tomita,et al: "Sequential activation of raf-1 kinase,MAP kinase kinase,MAP kinase,and S6 kinase by hyperosmolality in renal cells." J Biol Chem.269. 31296-31301 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] A.Owada,K.Tomita,et al: "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)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y Terada,K Tomita,et al: "Sequential activation of raf-1 kinase,MAP kinase kinase,MAP kinase,and S6 kinase by hyperosmolality in renal cells." J Biol Chem.269. 31296-31301 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] A.Owada,K.Tomita,et al: "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)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Terada,K.Tomita,et al: "Different localization and regulation of two types of vasoperssin receptor mRNA in microdissected rat nephron segments using reverse transcription polymerase chain reaction." J.Clin.Invest.92. 2339-2345 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Terada,K.Tomita,et al: "PCR localization of nitric oxide synthase and soluble guanylate cyclase mRNAs in microdissected rat nephron segments." J.Clin.Invest.90. 659-665 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Ujiie,K.Tomita,et al: "mRNA expression and synthesis of endothelin-1 along rat nephron segments." J.Clin.Invest.90. 1043-1048 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Yang,K.Tomita,et al: "Distribution of kallikrein-binding protein mRNA in kidneys and difference between SHR and WKY rats." Am.J.Physiol.267. F325-F330 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tomita.K.et al: "Effects of endothelin-1 on water and chloride transport in CCD of the rat" Am.J.Physiol. 264. F690-F696 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Terada.Y.et al: "Localization of type-1 AT-II receptor mRNA in out nephron segments" Kidney Int. 43. 1251-1259 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Terada,Y.et al: "Different localization and regulation of two types of AVP receptor mRNA" J.Clim.Invest. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Owada.A.et al: "ET-3 stimulates cGMP production in ET_B receptor" J.Clim.Invest. (in press).

    • Related Report
      1993 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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