Sphingosine induces phospholipase D and mitogen activated protein kinase in vascular smooth muscle cells

The enzymes phospholipase D and diacylglycerol kinase generate phosphatidic acid which is considered to be a mitogen. Here we report that sphingosine produced a significant amount of phosphatidic acid in vascular smooth muscl e cells from the rat aorta. The diacylglycerol kinase inhibitor R59 949 par tially depressed sphingosine induced phosphatidic acid formation, suggestin g that activation of phospholipase C and diacylglycerol kinase can not acco unt for the bulk of phosphatidic acid produced and that additional pathways such as phospholipase D may contribute to this. Further, we have shown tha t phosphatidylethanol was produced by sphingosine when vascular smooth musc le cells were stimulated in the presence of ethanol. Finally, as previously shown for other cell types, sphingosine stimulated mitogen-activated prote in kinase in vascular smooth muscle cells.