Platelet-activating factor modulates brain sphingomyelin metabolism.
In the present study the modulatory action of platelet-activating factor (PAF) on sphingolipid metabolism in cerebral cortical slices was studied. PAF did not alter the basal levels of either sphingomyelin (SM) or ceramide. However, the SMase-elicited reciprocal alterations in SM and ceramide levels were partially prevented by the PAF treatment. The PAF effect was dose-dependent, with 10-8 m being the lowest effective concentration, and receptor-mediated as it was abolished by WEB 2086, a PAF receptor antagonist. Neither N-oleoylethanolamine (OE, ceramidase inhibitor) or d,l-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP, an inhibitor of glucosylceramide synthase and the formation of 1-O-acyl ceramides) prevented the action of PAF. Therefore, the effect of PAF was unlikely to be dependent upon transformation of ceramides into glycosphingolipids, 1-O-acyl ceramides or sphingosine. Experiments with different labeled compounds ([14C]serine, [14C]arachidonate and phosphatidyl [N-methyl-3H]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 itself did not evoke any variation in the lipids analyzed but always prevented the SMase-evoked alterations. Together the data suggest the interesting possibility that PAF increases the overall turnover of SM. In summary, the present data demonstrate that PAF is able to regulate the cellular ceramide levels in brain by accelerating the SM cycle.
Latorre
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Departamento De Bioquimica y Biología Molecular I. Facultad de Químicas, Universidad Complutense de Madrid, Spain.
Aragonés
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MD
Fernández
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Catalán
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D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013109:Sphingomyelins / Q000378:metabolism*
D010972:Platelet Activating Factor; D013109:Sphingomyelins