Sphingosine-1-phosphate Induces Early Response Gene Expression in C6 Glioma Cells

Sphingosine-1-phosphate (S1P) caused dose-dependent and time-dependent increases in c-fos mRNA. Pretreatment with pertussis toxin (PTX; 100 ng/mlx24 h) reduced c-fos activation by S1P (100 microM-187+/-6% vs. 411+/-27%) and lysophosphatidic acid (LPA; 100 microM-90+/-34% vs. 188+/-41%), but not by sphingosylphosphorylcholine (SPC; 100 microM-390+/-47% vs. 420+/-44%). RT-PCR analysis and sequencing demonstrated the presence of previously unidentified LPA-responsive Endothelial Differentiation Gene (EDG) receptor mRNAs in C6 cells: EDG-2 and EDG-4.