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Mechanism of Biosynthesis and Secretion of Endothelin Family

Research Project

Project/Area Number 03454512
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionTokyo Medical and Dental University

Principal Investigator

HIRATA Yukio  Tokyo Medical and Dental University, School of Medicine, Associate Professor, 医学部, 助教授 (50135787)

Co-Investigator(Kenkyū-buntansha) MARUMO Fumiaki  Tokyo Medical and Dental University, School of Medicine, Professor, 医学部, 教授 (00050443)
七里 眞義  東京医科歯科大学, 医学部, 助手 (10206097)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1993: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1992: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1991: ¥3,200,000 (Direct Cost: ¥3,200,000)
KeywordsEndothelin / Regulation of Gene expression / Receptor subtype / Signal transduction / G-protein / レセプターアンタゴニスト / 心肥大 / 血管肥厚 / レセプター / 発現 / 局所因子 / ホルモン / エンドセリンー1 / レセプタ-サブタイプ / ホスホイノシト-ル / 細胞内Ca^<2+> / Cキナ-ゼ / 遺伝子発現 / 細胞増殖
Research Abstract

Objective of the present investigation was to elucidate 1)cellular mechanism by which endothelin-1 (ET-1) is synthesized by and released from vascular endothelial cells and nonvascular cells ; 2) different signal transdutions by endothelin family. ET-1 is constitutively secreted by endothelial and epithelial cells, which is regulated at the transcriptional level. Angiotensin and vasopressin induce phosphatidylinositol turnover to activate protein kinase C and elevate cytosolic calcium level, both of which cause important signals for transactivation of ET-1 gene in endothelial and epithelial cells. ET_A and ET_B receptors are coupled to phospholipase C via Gq protein in vascular smooth muscle cells and endothelial cells, respectively. ET_A receptor is also coupled to adenylate cyclase via Gs protein in vascular smooth muscle cells, while ET_B receptor is also coupled to adenylate cyclase via Gi protein in endothelial cells, suggesting that multiple G-proteins may mediate different sygnals. ET_B receptor in endothelium mediates synthesis of NO, whereas ET_B receptor in vascular smooth muscle, like ET_A receptor, mediates vasoconstriction as well as cell proliferation. Thus, ET receptor subtypes are involved in multiple cell functions via cross-talk of different signal tranduction systems.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Shichiri M et al: "Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines" J.Clin.Invest.87. 1867-1871 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Imai T et al: "Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells" Hypertension. 19. 753-757 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Eguchi S et al: "Endothelin receptor subtypes are coupled to adenylate cyclase via different G-proteins in vosculature" Endocrinology. 132. 524-529 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ito H et al: "Endothelin-1 is an autocrine/paracrine factor in the mechanism of angiotensin II-induced hypertrophy of cultured rat cordiomyocytes." J.Clin.Invest.92. 398-403 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hirata Y et al: "Endothelin receptor subtype B mediates synthesis of vitric oxide by cultured bovine endothelial cells" J.Clin.Invest.91. 1367-1373 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Emori T et al: "Cellular mechanism of natriuretic peptides-induced inhibition of endothelin-1 biosynthesis in rat endothelial cells." Endocrinology. 133. 2474-2480 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shichiri M et al: "Endothelin-1 is an autocrine/paracrine growth factor for human cancer lines" J.Clin. Invest.87. 1867-1971 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Imai T et al: "Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells" Hypertension. 19. 753-757 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Eguchi S et al: "Endothelin receptor subtypes are coupled to adenylate cyclase via different G-proteins in vasculature" Endocrinology. 132. 524-529 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ito H et al: "Endothelin-1 is an autocrine/paracrine factor in the mechanism of angiotensinII-induced hypertrophy of cultured rat condiomyocytes" J.Clin. Invest.92. 398-403 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hirata Y et al: "Endothelin receptor subtype B mediates sybthesis of nitric oxide by cultured bovine endothelial cells" J.Clin. Invest.91. 1367-1373 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Emori T et al: "Cellular mechanism of natriuretic peptides-induced inhibition of endothelin-1 biosynthesis in rat endothelial" Endocrinology. 133. 2474-2480 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Imai T et al: "Hepariu has an inhibitory effect on endothelin-1 syuthesis and release by endothelial cells" Hypertarsion. 21. 353-358 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Eguchi S et al: "Endothelin receptor subtypes are conpled to aderrylate cyclose via different G proteins in vosculature" Eudocrinology. 132. 524-529 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirata Y et al: "Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells." J Clin Invest. 91. 1367-1373 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ito H et al: "Endothelin-1 is an autocrive/paracrine factor in the mechanism of angiotensin II-induced hypertrophy of cultured rat cardiomyocytes" J Clin Invest. 92. 398-403 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirata Y et al: "Concomitant expression of endothelin receptor subtype and Bopeptides by pheochromocytome and bovine adrenal wedulla" Hypeiteusion Res. 16. 215-219 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Emori T et al: "Cellular mechanison of hatriuretic peptides-induced inhibition of endothelin-1 induced biosynthesis in rat endothelial cells" Endocrinology. 133. 2474-2480 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Imai,T.: "Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells." Hypertension. 19. 753-757 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Eguchi,S.: "Endothelin receptcrs in human parathyroid gland." Biochem.Biophys.Res.Commun.184. 1448-1455 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Miyasaka,N.: "Increased production of endothelin-1 in inflammatory avthritides." Arthritis Rheum.35. 397-400 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kamada,S.: "Direct effect of endothelin-1 on granulosa cells of porcine ovary." J.Endocrinol.134. 59-66 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kubota,T.: "Synthesis and release of endothelin-1 by human decidual cells." J.clin,Endocrinol. 75. 1230-1234 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Imai,T.: "Concomitant expression of receptor subtype and isopeptide of endothelin by human adrenal gland." Biochem.Bicphys.Res.Commun.182. 1115-1121 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Emori: "Endothelinー3 stimulates production of endotheliumderived nitric oxide via phoshoinostide breakdown" Biochem.Biophys.Res.Commun.174. 228-235 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Shichiri: "Endothelinー1 is an autocrine 1 paracrine growth factor for human cncer cell lines." J.Clin.Invest.87. 1867-1871 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Emori: "Celluar mechanism of endothelinー1 release by angiotensin and vasopressin" Hypertension. 18. 165-170 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] H.Ito: "Endothelinー1 induces hypertrophy with enchanced expression of muscle specific genes in cultured neonatol rat cardiomyocytes." cir.Res.69. 209-215 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Emori: "Endothelinー3 stimulates prostacyclin production in cultured bovine endothelial cells." J.Cardiovasc.Pharmacol.17(7). S140-S142 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S.Eguchi: "Identification of G proteinーcoupled endothelin receptors in cultured bovine endothelial cells." Biochem.Biophys.Res.Commun. 174. 1343-1346 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Hirata(eds H.Matsuo,H.Imura): "Peptide Regulation of Cardiovascular Function" Academic Press, 428 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Hirata(eds H.Imura,H.Matsuo,T.Masaki): "Atrial and Brain Natriuretic Peptides" Kodansha Scientific, 355 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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