Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes.
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.
Kotarsky
Knut
K
Division of Immunology, Department for Experimental Medical Science, Lund University, Lund, Sweden.
Boketoft
Ake
A
Bristulf
Jesper
J
Nilsson
Niclas E
NE
Norberg
Ake
A
Hansson
Stefan
S
Owman
Christer
C
Sillard
Rannar
R
Leeb-Lundberg
L M Fredrik
LM
Olde
Björn
B
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
D018076:DNA, Complementary; C512992:LPAR5 protein, human; D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D000242:Cyclic AMP