Ceramide enhances susceptibility of membrane phospholipids to phospholipase A(2) through modification of lipid organization in platelet membranes

The effects of ceramide on agonist-stimulated phospholipase A(2) (PLA(2)) a ctivity were studied in platelets. Cell-permeable C-6-ceramide (N-hexanoyls phingosine) exogenously added to platelet suspension enhanced U46619-stimul ated arachidonic acid release and lysophosphatidylcholine production. Treat ment of platelets with sphingomyelinase also led to an enhancement of the r elease. The enhanced arachidonic acid release by exogenous ceramide was com pletely inhibited by methyl arachidonyl fluorophosphonate, a cytosolic PLA( 2) inhibitor. However, U46619-stimulated PLA(2) activity was not significan tly potentiated by ceramide. These results suggest that enrichment of ceram ide in membranes causes modification of intermolecular organization, leadin g to increased susceptibility of substrate phospholipids to PLA(2).