Involvement of sphingolipids in the endothelin-1 signal transduction mechanism in rat brain

In cerebral cortex, endothelin-1 (ET-1) evoked a decrease of 40% in sphingomyelin (SM) levels together with an increase in both ceramide and glycosphingolipid (GSL) levels (100 and 56% respectively). These facts indicate that ET-1 increases sphingomyelinase activity and, possibly, activates the synthesis of GSL. By contrast, in cerebellum ET-1 seems to activate the hydrolysis of both SM and GSL, since the peptide evoked a decrease (near 30%) of their levels concomitantly with an increased production of ceramides (200%). These ceramides are clearly different from those produced in cerebral cortex which come from the SM hydrolysis only. It is suggested that ET B receptor subtype is involved in these responses.