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

Effects of FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol HC1), 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 previ...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1998, Vol.76(4), pp.377-385
Main Authors: Oyama, Yasuo, Chikahisa, Lumi, Kanemaru, Kaori, Nakata, Mami, Noguchi, Sachi, Nagano, Takayuki, Okazaki, Eisuke, Hirata, Akira
Format: Article
Language:eng ; jpn
Subjects:
Animals
Brain - cytology
Brain - drug effects
Brain neuron
Cytotoxic action
Digitoxin - pharmacology
Fingolimod Hydrochloride
Flow Cytometry
Fluorescent Dyes
Immunosuppressant
Immunosuppressive Agents - pharmacology
In Vitro Techniques
Neurons - drug effects
Neurons - metabolism
Propylene Glycols - pharmacology
Rats
Rats, Wistar
Spectrometry, Fluorescence
Sphingosine - analogs & derivatives
Thymocyte
Thymus Gland - cytology
Thymus Gland - drug effects
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Summary:Effects of FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol HC1), 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 μΜ deteriorated almost all of the thymocytes, while it was not the case for brain neurons. FTY720 increased the intracellular concentration of Ca2+ ([Ca2+]i) of thymocytes in both the presence and absence of external Ca2+, although the [Ca2+]i increased by FTY720 in the presence of external Ca2+ was much greater than that in the absence of external Ca2+. Thus, FTY720 may increase the membrane permeability of Ca2+ and release Ca2+ from intracellular Ca2+ 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 μΜ 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.
ISSN:0021-5198
1347-3506
DOI:10.1254/jjp.76.377