GPR17 does not couple to G12/13 signaling pathways. Cotransfection of the LPA1 receptor with PLC-ε (activated by Gα12/13) in COS-7 cells markedly increased LPA-promoted inositol phosphate accumulation, which was blocked by cotransfection of the RGS domain from p115RhoGEF. In contrast, LTC4 (100 nM) failed to promote significant inositol phosphate accumulation in COS-7 cells transfected with GPR17 or cotransfected with GPR17 and PLC-ε. GPR17-expressing cells were stimulated with 300 nM LTC4 (agonist, for 30 minutes), and all others were challenged with 10 μM LPA. Data shown are from a representative assay performed three times with similar results. cpm, counts per minute.