Abstract
In CHO cells stably expressing the GPR87 fused with a G16alpha protein, lysophosphatidic acid (LPA) evoked an intracellular Ca(2+) increase in a high affinity manner. The Ca(2+) 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites / genetics
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CHO Cells
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Calcium / metabolism*
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Cricetinae
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Cricetulus
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Electrophoresis, Polyacrylamide Gel
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Female
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GTP-Binding Protein alpha Subunits / genetics
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GTP-Binding Protein alpha Subunits / metabolism
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Gene Expression Profiling
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Humans
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Intracellular Fluid / drug effects
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Intracellular Fluid / metabolism
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Isoxazoles / pharmacology
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Lysophospholipids / metabolism
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Lysophospholipids / pharmacology
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Male
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Mice
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Mice, Inbred BALB C
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Models, Molecular
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Propionates / pharmacology
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Protein Structure, Tertiary
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RNA Interference
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Receptors, G-Protein-Coupled / chemistry
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism*
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Receptors, Lysophosphatidic Acid / antagonists & inhibitors
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Receptors, Lysophosphatidic Acid / genetics
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Receptors, Lysophosphatidic Acid / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Uridine Triphosphate / pharmacology
Substances
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3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid
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GPR87 protein, human
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GPR87 protein, mouse
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GTP-Binding Protein alpha Subunits
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Isoxazoles
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Lysophospholipids
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Propionates
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Receptors, G-Protein-Coupled
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Receptors, Lysophosphatidic Acid
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Recombinant Fusion Proteins
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lysophosphatidic acid
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Calcium
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Uridine Triphosphate