Sphingosine-1-phosphate (S1P) is a bioactive lipid signaling molecule, which plays an important role in many physiological processes like angiogenesis, vascular permeability, inflammation and immunity.

We investigated the influence of S1P on ionic currents in human macrophages (RAW cells) by means of the whole cell voltage clamp technique.

S1P activated outwardly rectifying currents. Their permeation characteristics depended on the extracellular anion species pointing to an activation of anion channels. This was supported by the similar pharmacological profile of S1P-induced currents and currents activated by hypotonic extracellular solution. Increasing the extracellular or decreasing the intracellular osmolarity inhibited the activation of the S1P-dependent current indicating that S1P activates volume-dependent channels. The effect of S1P was diminished by intracellular GDP-bS and by S1P receptor 1 (S1PR1) blockers.

Therefore we conclude that S1P acting on S1PR1 activates volume-dependent anion channels via a G-protein cascade.