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REGULATORY MECHANISMS OF VASCULAR CONTRACTION AND CELL PROLIFERATION IN DIABETES MELLITUS

Research Project

Project/Area Number 05837015
Research Category

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

Allocation TypeSingle-year Grants
Research Field 血管生物学
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

KOBAYASHI Sei  KYUSHU UNIVERSITY,FAC MED,ASSOC PROF, 医学部, 助教授 (80225515)

Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
KeywordsDiabetes Mellitus / Cell Proliferaton / Blood Vessel / Contraction / Smooth Muscle Cells / Calcium Ion / Cell Biology / Vasoactive Substances / 分子生物学
Research Abstract

The purpose of this research is to investigate the mechanisms of abnormal regulation of vascular contraction and cell proliferation in diabetes mellitus. The following results were obtained :
1.CELL PROLIFERATION OF VASCULAR SMOOTH MUSCLE CELLS.I developed the method to determine the phase of the cell cycle of vascular smooth muscle cells in primary culture at the single cell level. It was found that : (1)cytosolic Ca^<2+> transients are not required for platelet-derived growth factor (PDGF) to stimulate the cell cycle progression from the G_0 phase to the G_1 phase ; and (2)high glucose does not stimulate the cell cycle of the G_0 cells, whereas it stimulates the cell cycle of the PDGF-pretreated G_1 cells to the S and M phases, without any increase of cytosolic Ca^<2+> concentration ([Ca^<2+>]i).
2.CALCIUM TRANSIENTS OF ENDOTHELIAL CELLS.Using front-surface fluorometry and fura-2-loaded valvular endothelial cells in situ, it was found that : (1)endothelin-1 (ET-1) elevates [Ca^<2+>]i b … More y the stimulation of both Ca^<2+> influx and intracellular Ca^<2+> release ; and 2)the Ca^<2+>influx is regulated by an pertussis toxin-sensitive G-protein, while the release of intracellular Ca^<2+> is not.
3.VASCULAR CONTRACTION.(1)Using RT-PCR and fura-2 microfluorometry, it was found that angiotensin II (AT-II), protein kinase C,and protein Kinase A regulate the expression of AT-II receptor mRNA,and the increase in mRNA level is accompanied by an increase in physiological responsiveness. (2) Using fura-2-front-surface fluorometry and porcine coronary arterial strips, it was found that ET-3 induced vasoconstriction by increasing [Ca^<2+>]i mainly through the influx of extracellular Ca^<2+>, and that distinct mechanisms of time-dependent modulation of the Ca^<2+>-sensitivity function in the vasoconstrictor responses to ET-1 and ET-3. (3)It was found that norepinephrine induced increase in the Ca^<2+>-sensitivity of contractile apparatus, while serotonin demonstrates little enhancement of the Ca^<2+>-sensitivity of contractile apparatus. Less

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Aoki,H.: "Sensitivity of G-protein involved in endothelin-1-induced Ca^<2+> influx to pertussis toxin in porcine endothelial cells in situ." Br.J.Pharmacol.111. 989-996 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kobayashi,S.: "Cytosolic Ca^<2+> transients are not required for platelet-derived growth factor to induce cell cycle progression of vascular smooth muscle cells in primary culture:actions of tyrosine kinase." J.Biol.Chem.269. 9011-9018 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Chen,X.: "Protein kinase C and protein kinase A regulate the expression of angiotensin II receptor mRNA in smooth muscle cells." Eur.J.Pharmacol.267. 175-183 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ushio-Fukai,M.: "Endothelin-1 and endothelin-3 regulate differently vasoconstrictor responses of smooth muscle of the porcine coronary artery." Br.J.Pharmacol.114. 171-179 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fukuizumi,Y.: "Cytosolic calcium concentration-force relation during contractions in the rabbit femoral artery." Br.J.Pharmacol.114. 329-338 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyagi,Y.: "Resting load regulates cytosolic calcium-force relationship of the contraction of bovine cerebrovascular smooth muscle." J.Physiol.(London). (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Aoki H: "Sensitivity of G-protein involved in entothelin-1-induced Ca^<2+> influx to pertussis toxin in porcine endothelial cells in situ." Br.J.Pharmacol.111. 989-996 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kobayashi S: "Cytosolic Ca^<2+> transientsare not required for platelet-derived growth factor to induce cell cycle progression of vascular smooth muscle cells in primary culture : actions of tyrosine kinase." J.Biol.Chem.269. 9011-9018 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Chen X: "Protein kinase C and protein kinase A regulate the expression of angiotensin II receptor mRNA in smooth muscle cells." Eur.J.Pharmacol.267. 175-183 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ushio-Fukai M: "Endothelin-1 and endothelin-3 regulate differently vasoconstrictor responses of smooth muscle of the porcine coronary artery." Br.J.Pharmacol.114. 171-179 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fukuizumi Y: "Cytosolic calcium concentration-force relation during contractions in the rabbit femoral artery." Br.J.Pharmacol.114. 329-338 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyagi Y: "Resting load regulates cytosolic calcium-force relationship of the contraction of bovine cerebrovascular smooth muscle." J.Physiol. (London). (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Aoki,H.: "Sensitivity of G‐protein involved in endothelin‐1‐induced Ca^<2+>influx to pertussis toxin in porcine endothelial cells in situ." Br.J.Pharmacol.111. 989-996 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kobayashi,S.: "Cytosolic Ca^<2+> transients are not required for platelet‐derived growth factor to induce cell cycle progression of vascular smooth muscle cells in primary culture:actions of tyrosine kinase." J.Biol.Chem.269. 9011-9018 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Chen,X.: "Protein kinase Cand protein kinase A regulate the expression of angiotensin II receptor mRNA in smooth muscle cells." Eur.J.Pharmacol.267. 175-183 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ushio‐Fukai,M.: "Endothelin‐1 and endothelin‐3 regulate differently vasoconstrictor responses of smooth muscle of the porcine coronary artery." Br.J.Pharmacol.114. 171-179 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Fukuizumi,Y.: "Cytosolic calcium concentration‐force relation during contractions in the rabbit femoral artery." Br.J.Pharmacol.114. 329-338 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyagi,Y.: "Resting load regulates cytosolic calcium‐force relationship of the contraction of bovine cerebrovascular smooth muscle." J.Physiol.(London). (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Kuroiwa,M.: "Role of GTP-protein and endothelium in contraction induced by ethanol in pig coronary artery." J.Physiol.470. 521-537 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kai,T.: "Effects of lidocaine on intracellular C^<2+> and tension in airway smooth muscle." Anesthesiology. 78. 954-965 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ushio-Fukai,M.: "Effects of isoproterenol on cytosolic calcium concentration and on tension in the porcine coronary artery." J.Physiol.(London). 462. 679-696 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Aoki,H.: "G-protein involved in Ca^<2+>influx induced by endothelin-1 is sensitive to pertussis toxin in porcine endothelial cells in situ." Br.J.Pharmacol.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Aoki,H.: "Relationship between cytosolic calcium concentration and force in the papaverine-induced relaxation of medial strips of pig coronary artery." Br.J.Pharmacol.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Kobayashi,S.: "Cytosolic Ca^<2+> transients are not required for platelet-derived growth factor to induce cell cycle progression of vascular smooth muscle cells in primary culture:Action of tyrosine kinase." J.Biol.Chem.(in press).

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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