Identification of the orphan GPCR, P2Y(10) receptor as the sphingosine-1-phosphate and lysophosphatidic acid receptor

Biochem Biophys Res Commun. 2008 Jul 11;371(4):707-12. doi: 10.1016/j.bbrc.2008.04.145. Epub 2008 May 6.

Abstract

Phylogenetic analysis of transmembrane regions of GPCRs using PHYLIP indicated that the orphan receptor P2Y(10) receptor was classified into the cluster consisting nucleotide and lipid receptors. Based on the results, we studied the abilities of nucleotides and lipids to activate the P2Y(10) receptors. As a result, sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) evoked intracellular Ca(2+) increases in the CHO cells stably expressing the P2Y(10) fused with a G(16alpha) protein. These Ca(2+) responses were inhibited by S1P receptor and LPA receptor antagonists. The introduction of siRNA designed for P2Y(10) receptor into the P2Y(10)-CHO cells effectively blocked both S1P- and LPA-induced Ca(2+) increases. RT-PCR analysis showed that the mouse P2Y(10) was expressed in reproductive organs, brain, lung and skeletal muscle, suggesting the receptor plays physiological roles throughout the whole body. In conclusion, the P2Y(10) receptor is the first receptor identified as a dual lysophospholipid receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Calcium / metabolism
  • Cricetinae
  • Cricetulus
  • Humans
  • Ligands
  • Lysophospholipids / metabolism
  • Lysophospholipids / pharmacology
  • Mice
  • Molecular Sequence Data
  • Phylogeny
  • Protein Conformation
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Receptors, Lysophosphatidic Acid / classification*
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / physiology*
  • Receptors, Lysosphingolipid / classification*
  • Receptors, Lysosphingolipid / genetics
  • Receptors, Lysosphingolipid / physiology*
  • Receptors, Purinergic P2 / classification*
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, Protein
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism
  • Sphingosine / pharmacology
  • Tissue Distribution

Substances

  • Ligands
  • Lysophospholipids
  • P2Y10 protein, human
  • RNA, Small Interfering
  • Receptors, Lysophosphatidic Acid
  • Receptors, Lysosphingolipid
  • Receptors, Purinergic P2
  • sphingosine 1-phosphate
  • Sphingosine
  • lysophosphatidic acid
  • Calcium