Platelet-activating factor modulates brain sphingomyelin metabolism

In the present study the modulatory action of platelet-activating factor (P AF) on sphingolipid metabolism in cerebral cortical slices was studied. PAF did not alter the basal levels of either sphingomyelin (SM) or ceramide. H owever, the SMase-elicited reciprocal alterations in SM and ceramide levels were partially prevented by the PAF treatment. The PAF effect was dose-dep endent, with 10(-8) M being the lowest effective concentration, and recepto r-mediated as it was abolished by WEB 2086, a PAF receptor antagonist. Neit her N-oleoylethanolamine (OE, ceramidase inhibitor) or D,L-1-phenyl-2-decan oylamino-3-morpholin (PDMP, an inhibitor of glucosylceramide synthase and t he formation of 1-O-acyl ceramides) prevented the action of PAF. Therefore, the effect of PAF was unlikely to be dependent upon transformation of cera mides into glycosphingolipids, 1-O-acyl ceramides or sphingosine. Experimen ts with different labeled compounds ([C-14]serine, [C-14]arachidonate and p hosphatidyl [N-methyl-H-3]choline) were also performed to test whether PAF could affect the resynthesis of SM. Data obtained agree with the idea that selective pools of both choline and ethanolamine phospholipids were used as precursors for the resynthesis of SM elicited by SMase treatment. PAF itse lf did not evoke any variation in the lipids analyzed but always prevented the SMase-evoked alterations. Together the data suggest the interesting pos sibility that PAF increases the overall turnover of SM. In summary, the pre sent data demonstrate that PAF is able to regulate the cellular ceramide le vels in brain by accelerating the SM cycle.