Cytotoxic Actions of FTY720, a Novel Immunosuppressant, on Thymocytes and Brain Neurons Dissociated From the Rat

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Author(s)

    • Oyama Yasuo OYAMA Yasuo
    • Laboratory of Cellular Signalling, Faculty of Integrated Arts and Sciences, The University of Tokushima
    • NAKATA Mami
    • Laboratory of Cellular Signalling, Faculty of Integrated Arts and Sciences, The University of Tokushima
    • NOGUCHI Sachi
    • Laboratory of Cellular Signalling, Faculty of Integrated Arts and Sciences, The University of Tokushima
    • NAGANO Takayuki
    • Laboratory of Cellular Signalling, Faculty of Integrated Arts and Sciences, The University of Tokushima
    • OKAZAKI Eisuke
    • Laboratory of Cellular Signalling, Faculty of Integrated Arts and Sciences, The University of Tokushima
    • HIRATA Akira
    • Laboratory of Cellular Signalling, Faculty of Integrated Arts and Sciences, The University of Tokushima

Abstract

Effects of FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1, 3-propanediol HCl), a novel immunosuppressant, were examined on neurons and thymocytes respectively dissociated from rat brains and thymus glands using a flow cytometer to see if FTY720 exerts cytotoxic actions not only on spleen cells as previously reported but also on the other cells. FTY720 at a concentration of 10 μM deteriorated almost all of the thymocytes, while it was not the case for brain neurons. FTY720 increased the intracellular concentration of Ca<SUP>2+</SUP> ([Ca<SUP>2+</SUP>]<SUB>i</SUB>) of thymocytes in both the presence and absence of external Ca<SUP>2+</SUP>, although the [Ca<SUP>2+</SUP>]<SUB>i</SUB> increased by FTY720 in the presence of external Ca<SUP>2+</SUP> was much greater than that in the absence of external Ca<SUP>2+</SUP>. Thus, FTY720 may increase the membrane permeability of Ca<SUP>2+</SUP> and release Ca<SUP>2+</SUP> from intracellular Ca<SUP>2+</SUP> stores in thymocytes. Furthermore, the number of thymocytes stained with ethidium, a dye impermeant to intact membranes, time-dependently increased after drug application. Therefore, FTY720 at concentrations of 3 – 10 μM non-specifically increases the membrane permeability of thymocytes, resulting in necrotic cell death, although FTY720 at micromolar concentrations was reported to induce apoptosis of spleen cells.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 76(4), 377-385, 1998-04-01

    The Japanese Pharmacological Society

References:  22

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008192592
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4462594
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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