Delineation of the GPR15 receptor-mediated Gα protein signalling profile in recombinant mammalian cells.

The GPR15 receptor is a G protein-coupled receptor (GPCR), which is activated by an endogenous peptide GPR15L(25-81) and a C-terminal peptide fragment GPR15L(71-81). GPR15 signals through the G pathway to decrease intracellular cyclic adenosine 3',5'-monophosphate (cAMP). However, the activation profiles of the GPR15 receptor within G subtypes have not been examined. Moreover, whether the receptor can also couple to G , G and G is unclear. Here, GPR15L(25-81) and GPR15L(71-81) are used as pharmacological tool compounds to delineate the GPR15 receptor-mediated Gα protein signalling using a G protein activation assay and second messenger assay conducted on living cells. The results show that the GPR15 receptor preferentially couples to G rather than other pathways in both assays. Within the G family, the GPR15 receptor activates all the subtypes (G , G , G , G , G and G ). The E and activation rates of G G , G G and G are similar, whilst the E of G is smaller and the activation rate is significantly slower. The potencies of both peptides toward each G subtype have been determined. Furthermore, the GPR15 receptor signals through G to inhibit cAMP accumulation, which could be blocked by the application of the G inhibitor pertussis toxin.