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Intrarenal actions of atrial natriuretic peptides

Research Project

Project/Area Number 61570094
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionUniversity of Tokyo

Principal Investigator

ENDOU Hitoshi  Faculty of Medicine, University of Tokyo, 医学部, 助教授 (20101115)

Project Period (FY) 1986 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1986: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsAtrial natriuretic peptide / Rat single nephron / Collagenase / Collecting tubule / Prostaglandin E_2 / Cyclic GMP / Proximal tubule / 糖新生 / 単-ネフロン / プロスタグランジン【E_2】 / アラキドン酸
Research Abstract

Although atrial extracts and newly synthesized atrial natriuretic peptides (ANP) reveal a strong natriuretic effect, their intrarenal sites of action have not been clarified yet. This study was designed, therefore, to demonstrate the direct tubular effect(s) of ANP in rats, and to provide an evidence on a possible second messenger of ANP.
1) Atrial natriuretic peptide (5-28AA; ANP) and atrial extract (ANS) stimulated rat renal gluconeogenesis in cortical tubule suspension in a dose dependent fashion only from substrates that enter gluconeogenesis via phosphoenolpyruvate carboxylase. The effects of ANP and ANS were significantly poteneiated by cAMP and cGMP, whereas methoxamine showed no effect. Extracellular calcium revealed a key role for ANP and ANS response to gluconeogenesis:a concentration of calcium higher than 1 mM was essential. Isolated cells from cortex which lost cell membrane polarity by warming but responded solely to cAMP and cGMP showed no effect by ANP nor ANS. These data suggest that ANP or ANS may act mainly from the basolateral site in the proximal tubule cell and promote gluconeogenesis through cAMP and/or cGMP system.
2) Kidneys from male SD rats were treated with collagenase, and various parts of the nephron were microdissected. After incubation of individual nephron segments in Dulbecco minimal essential medium for 60 min at 37゜C, PGE_2 synthesized was quantified using RIA. PGE_2 producing activities were highly distributed in the medullary (MCT) and cortical collecting tubule (CCT). ANP (1-28AA) at 10^<-9> to 10^<-6>M increased PGE_2 production specifically in CCT, but not in MCT, indicating that ANP has a tubular effect in CCT on inhibiting NaCl reabsorption.
3) ANP increased cGMP contents in the glomerulus, CCT and MDT. Exogeneous cGMP (10^<-3>M) increased PGE_2 only in CCT up to the similar level by excess ANP, suggesting that cGMP could be a second messenger of ANP.

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Obara Tomoko: Biochem.Biophys.Res.Commun.129(3). 833-839 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Obara Tomoko: Jap.J.Nephrol. 28(7). 921-923 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Takemoto Fumi: Japan.J.Pharmacol.40. 203 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 遠藤仁: 東京医学. 93(4). 362-366 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Takemoto Fumi: Japan.J.Pharmacol.43. 129 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Endou Hitoshi: Contrib.Nephrol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 越川昭三,長沢俊彦,小磯謙吉,伊藤拓,遠藤仁編集: Annual Review腎臓1987. 382 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Sasaovongvivad,C.and Iwai,S.(Eds.);Endou Hitoshi: "Metabolic heterogeneity of memmalian naphrons:In Proc.JSPSNRCT Workshop,Clinical Pharmacology & Pharmacokinetics of cadiovascular and renal drugs." I.C.M.R,Kobe,Japan, 157 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Obara Tomoko: "Atrial natriuretic peptides stimulate renal gluconeogenesis." Biochem. Biophys. Res. Commun.129(3). 833-839 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Obara Tomoko: "A direct effect of atrial natriuretic peptides on the proximal tubule in rats." Jap. J. nephrol. 28(7). 921-923 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Endou Hitoshi: "Effects of atrial natriuretic peptides on tubular functions." Tokyo Med. Sci.93(4). 362-366 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Takemoto Fumi: "Increasing effects of atrial natriuretic peptide on prostaglandin E_2 production in rat collecting tubules." Japan J. Pharmacol.43. 129 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Endou Hitoshi: "Intranephron ammoniagenesis and its regulation by PGE_2 in rats and mice." Contrib. Nephrol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Endou Hitoshi: Metabolic heterogeneity of mammalian nephrons: In Proc. JSPS-NRCT Workshop, Clinical Pharmacology & Pharmacokinetics of cardiovascular and renal drugs.Sasaovongvivad, C. and Iwai, S. (Eds) I.C.M.R, Kobe, Japan, 157 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Obara Tomoko: Japanese Journal of Nephrology. 28. 921-923 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Yamada Hideo: Pfl【u!"】gers Archiv,European Journal of Physiology. 407. 1-7 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Nakanishi Taichi: Clinical and Experimental Hypertension,Theory and Practice. A8. 91-112 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Nakada Jojiro: Renal Physiology. 9. 213-222 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Nonoguchi Hiroshi: Pfl【u!"】gers Archiv,European Journal of Physiology. 407. 245-251 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 遠藤仁: 東京医学. 93. 362-366 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 遠藤仁: "医科薬理学" 南山堂(藤原元始,栗山欣弥,服部圭佑), 660 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Endou Hitoshi: "Nephrotoxicity of Antibiotics and Immunosuppressants" Elsevier Science Publishers Tanabe Tsuneyoshi,Jerry B.Hook,Endou Hitoshi, 250 (1986)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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