5-Nitro-2-(3-phenylpropylamino)benzoic acid is a GPR35 agonist

Pharmacology. 2008;82(4):245-9. doi: 10.1159/000157625. Epub 2008 Sep 26.

Abstract

GPR35 is a Gi/o- and G16-coupled receptor abundantly expressed in gastrointestinal tissues and immune cells. Kynurenic acid (a tryptophan metabolite and ionotropic glutamate receptor antagonist) and zaprinast (a phosphodiesterase inhibitor) are GPR35 agonists. Here, we show that the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) is also a GPR35 agonist. NPPB activates the GPR35-Gi/o and GPR35-G16 pathways in human embryonic kidney 293 (HEK293) cells and induces intracellular calcium mobilization in a concentration-dependent manner in HEK293 cells coexpressing human, rat or mouse GPR35 and the chimeric G protein G(qi5). These results suggest a novel pharmacological activity of NPPB and will provide useful information to search for more potent and selective GPR35 agonists.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Line
  • Chloride Channels / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • GTP-Binding Protein alpha Subunits, Gi-Go / drug effects
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / drug effects
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Humans
  • Kidney / cytology
  • Kidney / metabolism
  • Mice
  • Nitrobenzoates / administration & dosage
  • Nitrobenzoates / pharmacology*
  • Purinones / administration & dosage
  • Purinones / pharmacology
  • Rats
  • Receptors, G-Protein-Coupled / agonists*

Substances

  • Chloride Channels
  • GPR35 protein, human
  • GPR35 protein, mouse
  • GPR35 protein, rat
  • Nitrobenzoates
  • Purinones
  • Receptors, G-Protein-Coupled
  • 5-nitro-2-(3-phenylpropylamino)benzoic acid
  • G protein alpha 16
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • zaprinast