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 (KD = 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 LPA1-3 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.
Footnotes
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This work was supported by GS Development, the Segerfalk Foundation, Crafoord Foundation, Kock Foundation, Swedish Society for Medical Research, Royal Physiographic Society, the Juhlin Foundation, Medical Faculty at Lund University, and the Swedish Research Council. K.K. was supported by a postdoctoral fellowship financed by Swegene and the Wallenberg Foundation.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.098848.
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ABBREVIATIONS: GPCR, G protein-coupled receptor; IEL intraepithelial lymphocytes; LPA, lysophosphatidic acid; LPC, lysophosphatidylcholine; LPS, lysophosphatidylserine; LPE, lysophosphatidylethanolamine; LPG, lysophosphatidylglycerol; LPL, lamina propria lymphocytes; DGPP, diacylglycerol pyrophosphate; q, quantitative; RT, reverse transcription; PCR, polymerase chain reaction; PI, phosphoinositide; S1P, sphingosyl-1-phosphate; DMEM, Dulbecco's modified Eagle's medium; CHO, Chinese hamster ovary; FBS, fetal bovine serum; BSA, bovine serum albumin; PBS, phosphate-buffered saline; TCR, T-cell receptor.
- Received November 27, 2005.
- Accepted April 27, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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