Enhancement of sphingosine 1-phosphate-induced migration of vascular endothelial cells and smooth muscle cells by an EDG-5 antagonist

Biochem Biophys Res Commun. 2002 Dec 6;299(3):483-7. doi: 10.1016/s0006-291x(02)02671-2.


Sphingosine 1-phosphate (Sph-1-P), a bioactive lysophospholipid capable of inducing a wide spectrum of biological responses, acts as an intercellular mediator, through interaction with the endothelial differentiation gene (EDG)/S1P family of G protein-coupled receptors. In this study, the effects of JTE-013, a specific antagonist of the migration-inhibitory receptor EDG-5, on Sph-1-P-elicited responses were examined in human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (SMCs), which expressed EDG-5 protein weakly and abundantly, respectively. This pyrazolopyridine compound reversed the inhibitory effect of Sph-1-P on SMC migration and further enhanced Sph-1-P-stimulated HUVEC migration. In contrast, its effect on Sph-1-P-induced intracellular Ca(2+) mobilization was marginal. Our results indicate that specific regulation of Sph-1-P-modulated migration responses in vascular cells can be achieved by EDG-5 antagonists and that manipulation of Sph-1-P biological activities by each EDG antagonist may lead to a therapeutical application to control vascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Signaling / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Fluorescent Dyes / metabolism
  • Fura-2 / metabolism
  • Humans
  • Immediate-Early Proteins / metabolism
  • Lysophospholipids*
  • Muscle, Smooth, Vascular / cytology
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Pyrazoles / chemistry
  • Pyridines / chemistry
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophospholipid
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology*


  • Fluorescent Dyes
  • Immediate-Early Proteins
  • Lysophospholipids
  • Pyrazoles
  • Pyridines
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • pyrazolopyridine
  • sphingosine 1-phosphate
  • Sphingosine
  • Fura-2