Bradykinin increases ceramide and sphingosine content in human fibroblasts: possible involvement of glycosphingolipids.

Sphingolipid-derived products are recognized as second messengers able to mediate the action of extracellular signals such as cytokines and growth factors. In the present study it is shown that also bradykinin (BK), a pro-inflammatory peptide acting through G-protein-coupled receptors, is able to activate sphingolipid metabolism. Fibroblast treatment with the peptide provokes a rapid and significant increase in ceramide followed by a transient rise in sphingosine content. Sphingomyelin does not appear to be the source of ceramide since BK was unable to decrease the [3H]sphingomyelin pool and no increase in neutral or acidic sphingomyelinase activities could be detected after treatment with the peptide. The observation that the labeled glycosphingolipid pool is decreased upon BK stimulation would rather suggest that the peptide increases ceramide cellular content by rapidly mobilizing neutral glycolipids. Even though the physiological relevance of ceramide and sphingosine increase induced by BK is not known, it is noteworthy that glycosphingolipids may participate in this lipid signalling pathway.