title: Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes.
abstract: Here, the ligand binding, activation, and tissue distribution of the orphan G protein-coupled receptor (GPCR) GPR92 were studied. GPR92 binds and is activated by compounds based on the lysophosphatidic acid (LPA) backbone. The binding of LPA to GPR92 was of high affinity (K(D) = 6.4 +/- 0.9 nM) and led to an increase in both phosphoinositide hydrolysis and cAMP production. GPR92 is atypical in that it has a low sequence homology with the classic LPA(1-3) receptors (21-22%). Expression of GPR92 is mainly found in heart, placenta, spleen, brain, lung, and gut. Notably, GPR92 is highly expressed in the lymphocyte compartment of the gastrointestinal tract. It is the most abundant GPCR activated by LPA found in the small intestinal intraepithelial CD8+ cytotoxic T cells.
authors.affiliation: Division of Immunology, Department for Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Knut
authors.initials: K
authors.lastname: Kotarsky
authors.forename: Ake
authors.initials: A
authors.lastname: Boketoft
authors.forename: Jesper
authors.initials: J
authors.lastname: Bristulf
authors.forename: Niclas E
authors.initials: NE
authors.lastname: Nilsson
authors.forename: Ake
authors.initials: A
authors.lastname: Norberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Hansson
authors.forename: Christer
authors.initials: C
authors.lastname: Owman
authors.forename: Rannar
authors.initials: R
authors.lastname: Sillard
authors.forename: L M Fredrik
authors.initials: LM
authors.lastname: Leeb-Lundberg
authors.forename: Björn
authors.initials: B
authors.lastname: Olde
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004064:Digestive System / Q000166:cytology* / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D010802:Phylogeny; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects*; D049368:Receptors, Lysophosphatidic Acid / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; C512992:LPAR5 protein, human; D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D000242:Cyclic AMP