Nucleoside 5'-O-monophosphorothioates as modulators of the P2Y14 receptor and mast cell degranulation

Oncotarget. 2016 Oct 25;7(43):69358-69370. doi: 10.18632/oncotarget.12541.


Mast cells (MCs) are long-lived resident cells known for their substantial role in antigen-induced anaphylaxis and other immunoglobulin E-mediated allergic reactions as well as tumor promotion. MCs' activation results in the release of pro-inflammatory factors such as histamine, tryptase, tumor necrosis factor or carboxypeptidase A stored in secretory granules. IgE-dependent hypersensitivity has been thought to be the major pathway mediating degranulation of mast cells, but the P2Y14 nucleotide receptor activated by UDP-glucose (UDPG) may also enhance this process. In this study we identified thymidine 5'-O-monophosphorothioate (TMPS) as a molecule inhibiting UDPG-induced degranulation in a rat mast cell line (RBL-2H3). Additionally, TMPS diminished UDPG-evoked intracellular calcium mobilization in a stable HEK293T cell line overexpressing the P2Y14 receptor. Therefore, we demonstrate that the use of thymidine 5'-O-monophosphorothioate might be a novel anti-inflammatory approach based on preventingmast cell activation.

Keywords: Immune response; Immunity; Immunology and Microbiology Section; P2Y receptors; RBL-2H3 cells; degranulation; inflammation; nucleoside 5’-O-monophosphorothioates.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Degranulation / drug effects*
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Mast Cells / physiology
  • Rats
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism*
  • Signal Transduction / drug effects
  • Thionucleotides / chemistry
  • Thionucleotides / pharmacology*
  • Thymidine / chemistry
  • Thymidine / pharmacology
  • Uridine Diphosphate Glucose / pharmacology
  • beta-N-Acetylhexosaminidases / metabolism


  • P2Y14 receptor, human
  • Receptors, Purinergic P2
  • Thionucleotides
  • beta-N-Acetylhexosaminidases
  • Calcium
  • Uridine Diphosphate Glucose
  • Thymidine