Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35

FEBS Lett. 2006 Sep 18;580(21):5003-8. doi: 10.1016/j.febslet.2006.08.015. Epub 2006 Aug 17.


We found that zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, acted as an agonist for a G protein-coupled receptor, GPR35. In our intracellular calcium mobilization assay, zaprinast activated rat GPR35 strongly (geometric mean EC(50) value of 16nM), whereas it activated human GPR35 moderately (geometric mean EC(50) value of 840nM). We also demonstrated that GPR35 acted as a Galpha(i/o)- and Galpha(16)-coupled receptor for zaprinast when heterologously expressed in human embryonic kidney 293 (HEK 293) cells. These findings will facilitate the research on GPR35 and the drug discovery of the GPR35 modulators.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Cloning, Molecular
  • Gene Expression Profiling
  • Humans
  • Mice
  • Molecular Sequence Data
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / pharmacology*
  • Purinones / chemistry
  • Purinones / pharmacology*
  • Rats
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / chemistry
  • Sequence Alignment


  • GPR35 protein, human
  • GPR35 protein, rat
  • Phosphodiesterase Inhibitors
  • Purinones
  • Receptors, G-Protein-Coupled
  • zaprinast