title: 5-Nitro-2-(3-phenylpropylamino)benzoic acid is a GPR35 agonist.
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.
authors.affiliation: Discovery Biology Research, Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Inc., Taketoyo, Japan. Yasuhito.Taniguchi@pfizer.com
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tonai-Kachi
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Shinjo
mesh_terms: D000818:Animals; D002460:Cell Line; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009579:Nitrobenzoates / Q000008:administration & dosage / Q000494:pharmacology*; D011688:Purinones / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*
chemical_list: D018118:Chloride Channels; C111379:GPR35 protein, human; C513986:GPR35 protein, mouse; C513985:GPR35 protein, rat; D009579:Nitrobenzoates; D011688:Purinones; D043562:Receptors, G-Protein-Coupled; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C112631:G protein alpha 16; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; C011145:zaprinast