The orphan GPCR GPR87 was deorphanized and shown to be a lysophosphatidic acid receptor

Abstract: In CHO cells stably expressing the GPR87 fused with a G16α protein, lysophosphatidic acid (LPA) evoked an intracellular Ca2+ increase in a high affinity manner. The Ca2+ increase was reversibly blocked by the LPA receptor antagonists and inhibited by pretreatment of the cells with GPR87-specific siRNAs. GPR87 was shown to be closer to the P2Y and P2Y-related receptors than LPA receptors by ClustalW analyses. However, none of nucleotides and their derivatives activated GPR87. The human gpr87 is located on the chromosome 3q25 in a cluster containing p2y12,13,14. RT-PCR analysis showed that the mouse GPR87 was expressed in placenta, ovary, testis, prostate, brain, and skeletal muscle. The 3D model of GPR87–LPA complex indicated that the ligand interacted with R115 and K296 of GPR87, which are well conserved in the P2Y receptors. These results suggest that the GPR87 is a LPA receptor which evolved from a common ancestor of P2Y receptors. [Copyright &y& Elsevier]