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/ml×24 h) reduced c-fos activation by S1P (100 μM-187±6% vs. 411±27%) and lysophosphatidic acid (LPA; 100 μM-90±34% vs. 188±41%), but not by sphingosylphosphorylcholine (SPC; 100 μM-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.