Cultured granule cells and astrocytes from cerebellum differ in metabolizing sphingosine

Sphingosine metabolism was studied in primary cultures of differentiated ce rebellar granule cells and astrocytes, After a 2-h pulse with [C3-H-3]sphin gosine at different doses (0.1-200 nmol/mg of cell protein), both cell type s efficiently incorporated the long chain base; the percentage of cellular [H-3]sphingosine over total label incorporation was extremely low at sphing osine doses of (10 nmol/mg of cell protein and increased at higher doses. M ost of the [H-3]sphingosine taken up underwent metabolic processing by N-ac ylation, 1-phosphorylation, and degradation (assessed as (H2O)-H-3 released in the medium). The metabolic processing of exogenous sphingosine was extr emely efficient in both cells, granule cells and astrocytes being able to m etabolize, respectively, an amount of sphingosine up to 80- and 300-fold th e cellular content of this long chain base in 2 h, At the different doses, the prevailing metabolic route of sphingosine was different. At lower doses and in a wide dose range, the major metabolic fate of sphingosine was N-ac ylation. With increasing doses, there was first increased sphingosine degra dation and then increased levels of sphingosine-1-phosphate, The data demon strate that, in neurons and astrocytes, the metabolic machinery devoted to sphingosine processing is different, astrocytes possessing an overall highe r capacity to synthesize the bioactive compounds ceramide and sphingosine-1 -phosphate.