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1990 Fiscal Year Final Research Report Summary

Control of Membrane Permeability by External ATP in Animal Cells And its Application to Cancer Chemotherapy

Research Project

Project/Area Number 63571072
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research Institution国立予防衛生研究所

Principal Investigator

KITAGAWA Takayuki  Natl. Inst. Hlth, Dept. Chem., Section Chief, 化学部, 化学療法剤室長 (80092188)

Co-Investigator(Kenkyū-buntansha) AMANO Fumio  Natl. Inst. Hlth, Dept. Chem., Chief investigator, 化学部, 主任研究員 (90142132)
AKAMATSU Yuzuru  Natl. Inst. Hlth, Dept. Chem. Dept Hand, 化学部, 部長 (00072900)
Project Period (FY) 1988 – 1990
KeywordsMembrane permeability / ATP effect / Membrane variant / Calmodulin antagonists / Transformed cells / Cancer chemotherapy / がん化学療法
Research Abstract

External ATP causes the passive permeability change in several transformed cells but not in untransformed cells. The mechanism by which external ATP controls the permeability change and possible application of this phenomenon for the in vivo cancer chemotherapy have been examined in this research, and the following results were obtained :
1) The newly synthesized sulfonamide derivatives, which inhibit calmodulin-dependent phosphodiesterase activity, enhanced the ATP-dependent passive permeability change in CHO-K1 cells and B16 melanoma cells. The effective concentrations of these drugs were wider than those of previously known antagonists such as trifluoperazine and W7, suggesting the usefulness of the new drugs for pharmacological use.
2) Modulation of the membrane permeability with external ATP have been made in mildly alkaline Tris-buffered saline. Such increased membrane permeability with the ATP was also observed in B16 melanoma cells at pH 7.4 in a growth medium containing calf ser … More um and divalent ions at normal concentrations. Prolonged exposure of the transformed cells to the ATP in this medium led to cell lysis.
3) Studies on the two ATP-requiring enzyme activities, protein kinase and ATPase, present on the cell surface of CHO-K1 cells demonstrate that these ecto-enzymes are not directly associated with the ATP-dependent permeability change. However, several phosphorylated proteins were detected when the cells were permeabilized by external ATP and these protein phosphorylations were not observed in an ATP-resistant CHO clone. Further characteristics of these phosphoproteins are investigated.
4) Therapeutic effects of antitumor agents such as 5-FU and adriamycin against Ehrlich ascites cells grown in mouse ascites cavity or under the back skin were significantly enhanced by combined treatment with ATP. Similar results were also obtained with B16 melanoma cells. These results indicate the great usefulness of added ATP in the cancer chemotherapy management in vivo. Less

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] 北川 隆之: "動物細胞表面膜の細胞外ATPの透過性調節と化学療法への応用" 薬学雑誌. 108. 604-612 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北川 隆之: "物質透過性変化:特集「細胞測定法マニュアル」" 生体の科学. 39. 440-442 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takayuki Kitagawa,et al.: "External ATPーinduced passive permeability change and cell lysis:Action in serumーcontaining media." Biochim.Biophys.Acta(Biomembranes). 941. 257-263 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takayuki Kitagawa,et al.: "Inhibitory effects of newly synthesized sulfonamide derivatives on calmodulinーdependent phosphodiesterase activities and their modulation of ATPーdependent permeability change in mammalian cells." Biochim.Biophys.Acta(Biomembranes). 987. 235-238 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takayuki Kitagawa,et al.: "Regulation of glucose transport activity and expression of glucose transporter mRNA by serum,growth factors and phorbol ester in mouse fibroblasts." Biochim.Biophys.Acta(Biomembranes). 980. 100-108 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masaaki Iwaki,et al.: "Cytotoxic effects of aflatoxin Bl and its association with cellular components in chicken primary cultured cells." Biochim.Biophys.Acta(General subjects). 1035. 146-153 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北川 隆之: "動物細胞の増殖調節機構に関与する遺伝子の解析:増殖因子による糖輸送・輸送体遺伝子発現の調節機構." ビオメディカ. 5. 76-81 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takayuki Kitagawa,et al.: "Transforming growth factor Bl stimulates glucose transport and expression of glucose transporter mRNA in quiescent mouse fibroblasts." (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nobuo Yokoo,et al.: "Enhancing effect of external ATP on in vivo cytotoxicity of antitumor drugs for tranformed cells." (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北川 隆之,他(共訳): "生体膜:分子構造と機能(ロバ-トB.ゲニス著:Biomembranes)" シュプリンガ-フェアラ-ク社, 526 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitagawa, T.: "Control of membrane permeability by external ATP in animal cells and its application to chemotherapy." Yakugaku Zasshi. 108(7). 604-612 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, T.: "Changes in membrane permeability in animal cells." Seitai-no-Kagaku. 39 (5). 440-442 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, T., Amano , E. and Akamatsu, Y.: "External ATP-induced passive permeability change and cell lysis. Action in serum-containing media." Biochim. Biophys. Acta. 941. 257-263 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, T., et al.: "Inhibitory effects of newly synthesized sulfonamide derivatives on calmodulin dependent phosphodiestrase activities and their modulation of ATP-dependent permeability change in mammalian cells." Biochim. Biophys. Acta. 987. 235-238 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, T., et al.: "Regulation of glucose transport activity and expression of glucose transporter mRNA by serum, growth factors and phorbol ester in mouse fibroblasts." Biochim. Biophys. Acta. 980. 100-108 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwaki, M., Kitagawa, T., et al.: "Cytotoxic effects of aflatoxin B1 and its association with cellular components in chicken primary cultured cells." Biochim. Biophys. Acta. 1035. 146-153 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, T.: "Studies on cellular genes associated with growth control of animal cells. Control of glucose transport and the transporter gene expression by growth factors." Biomedical. 5 (10). 76-81 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, T., et al.: "Transforming growth factor B1 stimulates glucose transport and expression of glucose transporter mRNA in quiescent mouse fibroblasts." (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokoo, N., Kitagawa, T., et al.: "Enhancing effect of the in vivo cytotoxicity of antitumor drugs for transformed cells." (1991)

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

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Published: 1993-08-12  

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