In CHO cells stably expressing the GPR87 fused with a G(16 alpha) 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-rektted receptors than LPA receptors by ClustalW analyses. However, none of nucleoticles and their derivatives activated GPR87. The human gpr87 is located on the chromosome 3q25 in a cluster containing p2y(12,13,14). 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 R 115 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. (C) 2007 Elsevier Inc. All rights reserved.