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1999 Fiscal Year Final Research Report Summary

Secretory actions of volume-regulated chloride channel in vascular endothelial cells.

Research Project

Project/Area Number 10670087
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

OIKE Masahiro  Kyushu University, Graduate School of Medical Sciences, Lecturer, 大学院・医学系研究科, 講師 (70271103)

Project Period (FY) 1998 – 1999
KeywordsEndothelium / Mechanical stress / ATP / Chloride channel / Calcium
Research Abstract

Vascular endothelium is known to secrete various biologically active mediators in response to mechanical stress. However, the pathways for secreting these agents are still not clarified. On the other hand, volume-regulated chloride channel (VRAC) is activated by mechanical stress, especially hypotonic stress, in vascular endothelium. The aim of this study was to investigate the possible relationship between the activation of VRAC and the secretion of biological mediators. Hypotonic stress (HTS) elicited CaィイD12+ィエD1 oscillations in bovine aortic endothelial cells, which was suppressed by phospholipase C inhibitors and PィイD22ィエD2 antagonist, thereby suggesting the involvement of ATP release in HTS-induced CaィイD12+ィエD1 oscillations. The amount of ATP release was 91amol/cell/10min. On the other hand, HTS induced the activation of VRAC current, which was inhibited by high concentrations of glibenclamide, fluoxetine and verapamil. These agents also abolished HTS-induced CaィイD12+ィエD1 oscillations and ATP release. Furthermore, high KィイD1+ィエD1 depolarization also inhibited VRAC and CaィイD12+ィエD1 oscillations/ATP release. These suggest that ATP release largely depends on the activation of VRAC. However, previous reports have indicated that VRAC is inhibited by extracellular ATP, therefore ATP has been considered as an inhibitor of VRAC. We also observed that extracellular ATP blocked VRAC current, but its blocking action was less prominent at highly depolarized membrane potentials. By the mathematical analysis of these data, we succeeded to show that ATP has dual actions on VRAC, I. E., ATP partially blocks but partially permeates VRAC. Therefore, present study strongly suggests that HTS-induced ATP release is probably through VRAC.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Chiwaka Kimura: "Acute glucose overload abolishes Ca^< 2+> oscillation in cultured endothelial cells from bovine aorta: a possible role of superoxide anion."Circulation Research. 82巻. 677-685 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chiwaka Kimura: "Effects of acute glucose overload on histamine H_< 2> receptor-mediated Ca_< 2+> mobilization in bovine cerebral endothelial cells"Diabetes. 47巻. 104-112 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masahiro Oike: "Increase in calcium in smooth muscle cells of the rabbit bladder induced by acetylcholine and ATP."Journal of Autonomic Nervous System. 69巻. 141-147 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tetsuya Koyama: "Superoxide anion impairs Ca_< 2+> mobilization in cultured human nasal epithelial cells."American Journal of Physilogy. 277巻. L1089-L1095 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yeping Wang: "Effects of superoxide anion on intracellular Ca_< 2+> concentration in rabbit pulmonary arterial smooth muscle cells"Acta Pharmacologica Sinica. 20巻. 10-14 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masahiro Oike: "Hypotonic stress-induced dual Ca_< 2+> responses in bovine aortic endothelial cells"American Journal of Physilogy. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masahiro Oike: "Cell Volume Regulation (分担執筆)"Elsevier Science B. V.. 214 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chiwaka Kimura, Masahiro Oike, Yushi Ito: "Acute glucose overload abolishes CaィイD12+ィエD1 oscillation in cultured endothelial cells from bovine aorta : a possible role of superoxide anion."Circulation Research. 82(6). 677-85 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chiwaka Kimura, Masahiro Oike, Seizaburo Kashiwagi, Yushi Ito: "Efficts of acute glucose overload on histamine HィイD22ィエD2 receptor-mediated CaィイD12+ィエD1 mobilization in bovine cerebral endothelial cells."Diabetes. 47(1). 104-112 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masahiro Oike, Kate E. Creed, Hitoshi Onoue, Hiroyuki Tanaka, Yushi Ito: "Increase in calcium in smooth muscle cells of the rabbit bladder induced by acetylcholine and ATP."Journal of Autonomic Nervous System. 16(2-3). 141-147 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tetsuya Koyama, Masahiro Oike, Sohtaro Komiyama, Yushi Ito: "Superoxide anion impairs CaィイD12+ィエD1 mobilization in cultured human nasal epithelial cells."American Journal of Physiology. 277(6). L1089-L1095 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yeping Wang, Masahiro Oike, Yushi Ito: "Effects of superoxide anion on intracellular CaィイD12+ィエD1 concentration in rabbit pulmonary arterial smooth muscle cells."Acta Pharmacologica Sinica.. 20(1). 10-14 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masahiro Oike, Chiwaka Kimura, Tetsuya Koyama, Miyuki Yoshikawa, Yushi Ito: "Hypotonic stress-induced dual CaィイD12+ィエD1 responses in bovine aortic endothelial cells."American Journal of Physiology. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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