Actions of a picomolar short-acting S1P₁ agonist in S1P₁-eGFP knock-in mice

Nat Chem Biol. 2011 May;7(5):254-6. doi: 10.1038/nchembio.547. Epub 2011 Mar 27.

Abstract

Sphingosine 1-phosphate receptor 1 (S1P(1)) is critical for lymphocyte recirculation and is a clinical target for treatment of multiple sclerosis. By generating a short-duration S1P(1) agonist and mice in which fluorescently tagged S1P(1) replaces wild-type receptor, we elucidate physiological and agonist-perturbed changes in expression of S1P(1) at a subcellular level in vivo. We demonstrate differential downregulation of S1P(1) on lymphocytes and endothelia after agonist treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Down-Regulation / drug effects
  • Endothelium / drug effects
  • Endothelium / metabolism
  • Flow Cytometry
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • Gene Knock-In Techniques*
  • Green Fluorescent Proteins / chemistry*
  • Green Fluorescent Proteins / metabolism
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Mice
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
  • Receptors, Lysosphingolipid / agonists*
  • Receptors, Lysosphingolipid / metabolism
  • Receptors, Lysosphingolipid / therapeutic use*
  • Time Factors

Substances

  • Fluorescent Dyes
  • Receptors, Lysosphingolipid
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins

Associated data

  • PubChem-Substance/112629136
  • PubChem-Substance/112629137
  • PubChem-Substance/112629138
  • PubChem-Substance/112629139
  • PubChem-Substance/112629140