Sphingosine 1-phosphate stimulates Na+/H+ exchange in thyroid FRTL-5 cells.
Sphingosine derivatives are potent mitogens in several cell types. Many mitogens activate the Na+/H+ exchange, although the interrelationships between Na+/H+ exchange and mitogenesis are unclear. The present investigation in thyroid FRTL-5 cells shows that sphingosine 1-phosphate (SPP) activates Na+/H+ exchange in a dose-dependent manner in acid-loaded cells. The effect of SPP was abolished in a Na+-free buffer and by pretreatment of the cells with ethylisopropylamiloride. SPP did not affect basal intracellular pH (pHi). SPP stimulated the release of sequestered Ca2+ and a substantial entry of Ca2+. The effect of SPP on pH(i) was abolished in cells incubated in a Ca2+-free buffer, and in cells loaded with the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Furthermore, the effect of SPP was abolished in pertussis toxin (PTX)-treated cells. PTX decreased Ca2+ entry only, without affecting the release from intracellular stores. Phosphatidic acid (PA) did not activate Na+/H+ exchange, suggesting that the effect of SPP was not mediated via activation of phospholipase D and the production of PA. Thus one mechanism of action of SPP in FRTL-5 cells appears to be to activate Na+/H+ exchange. This action is mediated via a G protein-dependent mechanism and requires an increase in intracellular free Ca2+.
Törnquist
K
K
Department of Biosciences, University of Helsinki, Finland.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008246:Lysophospholipids; D037342:Pertussis Toxin; D010712:Phosphatidic Acids / Q000494:pharmacology; D010739:Phospholipase D / Q000502:physiology; D051381:Rats; D012964:Sodium / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D008246:Lysophospholipids; D010712:Phosphatidic Acids; D010566:Virulence Factors, Bordetella; C060506:sphingosine 1-phosphate; D012964:Sodium; D037342:Pertussis Toxin; D010739:Phospholipase D; D019204:GTP-Binding Proteins; D013110:Sphingosine; D002118:Calcium