DL-threo-Dihydrosphingosine is an inhibitor of Sphk (sphingosine kinase). This inhibitory activity has been employed as a tool for identifying the activity of sphingosine kinase in various processes. A role of sphingosine-1-phosphate generated by sphingosine kinase is suggested in the mobilization of Ca2+ stimulated by local discrete increases in intracellular Ca2+ at m2 and m3 muscarinic acetylcholine receptors. DL-threo-Dihydrosphingosine demonstrates inhibition of Ca2+ mobilization, and modulation of this process is suggested to function as an amplification for Ca2+ signals mediated by sphingosine kinase activity. The extracellular signal-regulated kinase (ERK) pathway is inhibited by DL-threo-Dihydrosphingosine, suggesting participation of sphingosine kinase in this pathway. DL-threo-Dihydrosphingosine was demonstrated to increase the sensitivity of HEK-293 cells to fumonisin B1cytotoxicity, indicating that fumonisin B1 resistance in HEK-293 cells involves rapid formation of sphingosine-1-phosphate by sphingosine kinase which confers survival properties to the cells.
