Effect of sphingosine derivatives on calcium fluxes in thyroid FRTL-5 cells.
The effects of sphingosine derivatives on Ca2+ fluxes were investigated in thyroid FRTL-5 cells labelled with Fura 2. Addition of sphingosylphosphocholine (SPC) or sphingosine (SP) increased intracellular free Ca2+ ([Ca2+]i) in a dose-dependent manner. At the highest dose tested (30 microM), the response was biphasic: a rapid transient increase in [Ca2+]i, followed by a new, elevated, level of [Ca2+]i. Both phases of the SPC-evoked increase in [Ca2+]i were dependent on extracellular Ca2+, whereas only the SP-evoked elevated level of [Ca2+]i was dependent on the influx of Ca2+. Both compounds released sequestered Ca2+ from thapsigargin- and inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ pools. In addition, the increase in [Ca2+]i in response to SPC, but not to SP, was attenuated in cells treated with phorbol myristate acetate or with the putative Ca(2+)-channel blocker SKF 96365, and in cells pretreated with pertussis toxin for 24 h. SPC did not activate the production of IP3. Furthermore, both SPC and SP released sequestered Ca2+ from permeabilized cells. We observed that SPC, but not SP, stimulated release of [3H]arachidonate from cells prelabelled with [3H]arachidonate for 24 h. Both SPC and SP stimulated the incorporation of [3H]thymidine into DNA in cells grown in the absence of thyroid-stimulating hormone (TSH). The results suggest that sphingosine derivatives are putative regulators of Ca2+ fluxes in FRTL-5 cells, and that SP and SPC may act on [Ca2+]i via different mechanisms. Furthermore, both SP and SPC may be of importance in modulating thyroid-cell proliferation.
Törnquist
K
K
Department of Zoology, University of Helsinki, Finland.
Ekokoski
E
E
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D008934:Mitogens / Q000494:pharmacology; D037342:Pertussis Toxin; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D008934:Mitogens; D010566:Virulence Factors, Bordetella; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D016718:Arachidonic Acid; D037342:Pertussis Toxin; D011493:Protein Kinase C; D013110:Sphingosine; D002118:Calcium