Extracellular release of newly synthesized sphingosine-1-phosphate by cerebellar granule cells and astrocytes

Viviana Anelli, Rosaria Bassi, Guido Tettamanti, Paola Viani, Laura Riboni

Research output: Contribution to journalArticlepeer-review


Sphingosine-1-phosphate (S1P) is a potent biomediator that can act as either an intracellular or an intercellular messenger. In the nervous system it exerts a wide range of actions, and specific membrane receptors for it have been identified in various regions. However, the physiological origin of extracellular S1P in the nervous system is largely unknown. We investigated cerebellar granule cells at different stages of differentiation and astrocytes in primary cultures as possible origins of extracellular S1P. Although these cells show marked differences in S1P metabolism, we found that they can all release S1P and express mRNAs for S1P specific receptors. Extracellular S1P derives from the export of newly synthesized intracellular S1P, and not from the action of a released sphingosine kinase. S1P release is rapid, efficient, and can be regulated by exogenous stimuli. Phorbol ester treatment resulted in an increase in sphingosine kinase 1 activity in the membranes, accompanied by a significant increase in extracellular S1P. S1P release in cells from the cerebellum emerges as a regulated mechanism, possibly related to a specific pool of newly synthesized S1P. To our knowledge, this is the first evidence of the extracellular release of S1P by primary cells from the CNS, which supports a role of S1P as autocrine/ paracrine physiological messenger in the cerebellum.

Original languageEnglish
Pages (from-to)1204-1215
Number of pages12
JournalJournal of Neurochemistry
Issue number5
Publication statusPublished - Mar 2005


  • Astrocytes
  • Cerebellar granule cells
  • Intercellular mediators
  • Sphingosine kinase
  • Sphingosine-1-phosphate

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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