Photolysis of intracellular caged sphingosine-1-phosphate causes Ca2+ mobilization independently of G-protein-coupled receptors

FEBS Lett. 2003 Nov 20;554(3):443-9. doi: 10.1016/s0014-5793(03)01219-5.


Sphingosine-1-phosphate (S1P), the product of sphingosine kinase, activates several widely expressed G-protein-coupled receptors (GPCR). S1P might also play a role as second messenger, but this hypothesis has been challenged by recent findings. Here we demonstrate that intracellular S1P can mobilize Ca(2+) in intact cells independently of S1P-GPCR. Within seconds, S1P generated by the photolysis of caged S1P raised the intracellular free Ca(2+) concentration in HEK-293, SKNMC and HepG2 cells, in which the response to extracellularly applied S1P was either blocked or absent. Ca(2+) transients induced by photolysis of caged S1P were caused by Ca(2+) mobilization from thapsigargin-sensitive stores. These results provide direct evidence for a true intracellular action of S1P.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / chemistry
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cell Line
  • Humans
  • Intracellular Space / chemistry*
  • Lysophospholipids*
  • Microscopy, Fluorescence / methods
  • Organophosphates / chemistry
  • Organophosphates / metabolism*
  • Photolysis
  • Receptors, G-Protein-Coupled / metabolism*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / chemistry
  • Sphingosine / metabolism*
  • Sphingosine / pharmacology*
  • Thapsigargin / pharmacology


  • Lysophospholipids
  • Organophosphates
  • Receptors, G-Protein-Coupled
  • caged sphingosine 1-phosphate
  • sphingosine 1-phosphate
  • Thapsigargin
  • Sphingosine
  • Calcium