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 muscle cells from the rat aorta. The diacylglycerol kinase inhibitor R59 949 partially depressed sphingosine induced phosphatidic acid formation, suggesting that activation of phospholipase C and diacylglycerol kinase can not account for the bulk of phosphatidic acid produced and that additional pathways such as phospholipase D may contribute to this. Further, we have shown that phosphatidylethanol was produced by sphingosine when vascular smooth muscle cells were stimulated in the presence of ethanol. Finally, as previously shown for other cell types, sphingosine stimulated mitogen-activated protein kinase in vascular smooth muscle cells.
Taher
M M
MM
Department of Anatomy and Surgery, Virginia Commonwealth University, Richmond 23298, USA. mtaher@hsc.vcu.edu
Abd-Elfattah
A S
AS
Sholley
M M
MM
D000818:Animals; D001011:Aorta; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D019852:Diacylglycerol Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D020404:Glycerophospholipids / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D052999:Quinazolinones; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
D020404:Glycerophospholipids; D010712:Phosphatidic Acids; D010880:Piperidines; D011799:Quinazolines; D052999:Quinazolinones; C051521:phosphatidylethanol; C058544:R 59949; D000431:Ethanol; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010738:Type C Phospholipases; D010739:Phospholipase D; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate