GPR35 Receptor Antibodies

Although GPR35 is still considered an orphan receptor, there have been attempts to deorphanize it by identifying endogenous molecules that can activate the receptor. All of the currently proposed ligands are either unselective towards GPR35, or they lack high potency, a characteristic feature of natural ligands.Kynurenic acid was first reported as an agonist of GPR35, but controversy remains whether the endogenous ligand reaches sufficient tissue concentrations to activate the receptor. 2-Acyl lysophosphatidic acid (2-oleoyl-LPA) has also been proposed as an endogenous ligand but these results were not replicated in a recent β-arrestin assay. Zaprinast, a cyclic GMP-selective phosphodiesterase (PDE5A/PDE6) inhibitor, has become widely used as a surrogate agonist to investigate GPR35 pharmacology and signalling. GPR35 is also activated by the loop diuretic drugs bumetanide and furosemide and the pharmaceutical adjunct pamoic acid. GPR35 is expressed by dendritic cells, macrophages, and granulocytes, all of which show chemotactic response to CXCL17. It is unclear whether the migration stimulatory response to CXCL17 is mediated by direct interaction with GPR35. GPR35 desensitization, β-arrestin recruitment and internalization are regulated by phosphorylation of carboxyl-terminal serine300/serine303 (pS300/pS303-GPR35). This nomenclature refers to the human GPR35 receptor. The mouse GPR35 receptor is related by phosphorylation of carboxyl-terminal serine298/serine301 (pS298/pS301-mGPR35) and serine305 (pS305-mGPR35). For more information on GPR35 pharmacology please refer to the IUPHAR database. For further reading refer to:

Davenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga CP, Bonner TI, Neubig RR, Pin JP, Spedding M, Harmar AJ. International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol Rev. 2013 May 17;65(3):967-86. doi: 10.1124/pr.112.007179. PMID: 23686350; PMCID: PMC3698937.

Divorty N, Jenkins L, Ganguly A, Butcher AJ, Hudson BD, Schulz S, Tobin AB, Nicklin SA, Milligan G. Agonist-induced phosphorylation of orthologues of the orphan receptor GPR35 functions as an activation sensor. J Biol Chem. 2022 Mar;298(3):101655. doi: 10.1016/j.jbc.2022.101655. Epub 2022 Jan 29. PMID: 35101446; PMCID: PMC8892012.