Sphingosine enhances phosphatidylinositol 4-kinase activity in rabbit platelets

J Biochem. 1996 Jul;120(1):61-5. doi: 10.1093/oxfordjournals.jbchem.a021394.


The modulating effect of sphingosine on the metabolism of inositol phospholipids was investigated using rabbit platelets. When [3H]arachidonic acid- or [3H]inositol-labeled platelets were incubated at 37 degrees C with sphingosine, the radioactivity of the phosphatidylinositol (PI) fraction obtained on TLC decreased time-dependently up to 5 min, and phosphatidylinositol monophosphate (PIP) and phosphatidylinositol bisphosphate (PIP2) increased concomitantly, though neither arachidonic acid nor 1,2-diacylglycerol was formed. The effect of sphingosine was dose-dependent, the maximum effect being observed at 20 microM. Treatment with a sphingosine derivative, sphingosine-1-phosphate (Sph-1-P) or N-hexanoyl-sphingosine (C6-ceramide), did not result in an increase in PIP. The increased radioactivity of PIP with sphingosine was attributable to an increase in phosphatidylinositol 4-phosphate, but not phosphatidylinositol 3-phosphate. Furthermore, wortmannin, an inhibitor of PI 3-kinase, did not affect the modulating effect of sphingosine at 100 nM, at which the enzyme is known to be completely inhibited. The activity of PI 4-kinase in the platelet lysate was increased by sphingosine but not by Sph-1-P. These results suggest that sphingosine enhances the activity of PI 4-kinase and thereby contributes to the regulation of inositol phospholipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • 1-Phosphatidylinositol 4-Kinase
  • Androstadienes / pharmacology
  • Animals
  • Arachidonic Acid / blood
  • Blood Platelets / enzymology*
  • Ceramides / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Lysophospholipids*
  • Phosphatidylinositol 3-Kinases
  • Phosphatidylinositols / blood
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / blood*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology
  • Rabbits
  • Sphingosine / analogs & derivatives
  • Sphingosine / pharmacology*
  • Staurosporine / pharmacology
  • Wortmannin


  • Androstadienes
  • Ceramides
  • Enzyme Inhibitors
  • Lysophospholipids
  • Phosphatidylinositols
  • sphingosine 1-phosphate
  • Arachidonic Acid
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-Phosphatidylinositol 4-Kinase
  • Protein Kinase C
  • Staurosporine
  • Sphingosine
  • Wortmannin