G protein-coupled receptors provide attractive targets for drug therapy due to the sheer size and diversity of ligands within this receptor family. G protein-coupled receptor (GPR) GPR41 and GPR43 are related members of a homologous family of orphan G protein-coupled receptors that are tandemly encoded at a single chromosomal locus in both humans and mice. GPR43 functions as a ligand for short chain fatty acids (SCFAs), notably acetate and propionate. Bacteria in the gut produce high concentrations of SCFAs, which are subsequently released in the bloodstream, where they exert cellular effects on blood leukocytes, including calcium release, ERK1/2 activation, and inhibition of cAMP accumulation. These effects indicate a role for GPR43 in the recruitment of leukocytes, particularly polymorphonuclear cells, to sites of bacterial infection.
