RT Journal Article SR Electronic T1 Expression and Characterization of a 5-oxo-6E,8Z,11Z,14Z-Eicosatetraenoic Acid Receptor Highly Expressed on Human Eosinophils and Neutrophils JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 471 OP 477 DO 10.1124/mol.63.3.471 VO 63 IS 3 A1 Carol E. Jones A1 Suzanne Holden A1 Laurent Tenaillon A1 Umesh Bhatia A1 Klaus Seuwen A1 Pamela Tranter A1 Jonathan Turner A1 Rachel Kettle A1 Rochdi Bouhelal A1 Steven Charlton A1 N. R. Nirmala A1 Gabor Jarai A1 Peter Finan YR 2003 UL http://molpharm.aspetjournals.org/content/63/3/471.abstract AB Using a bioinformatics approach, we have isolated a novel G-protein-coupled receptor (GPCR), R527, and have demonstrated that this receptor shows no significant homology to previously deorphanized GPCRs. Quantitative reverse transcription-polymerase chain reaction analysis of the expression of GPCR R527 indicated a very high level of mRNA expression in eosinophils, with high expression also detected in neutrophils and lung macrophages. Stable cell lines were generated expressing this receptor together with the G-protein α-subunit Gα16. These cells were used to screen an agonist collection in a calcium mobilization assay and 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) was identified as a putative ligand. 5(S)-Hydroxyperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid was also shown to activate the receptor, whereas the leukotrienes LTB4, LTC4, LTD4, and LTE4 failed to elicit a response. In cAMP assays, pertussis toxin reversed the inhibitory effects of 5-oxo-ETE on cAMP production, indicating that the receptor is Gαi-coupled. The GPCR R527 shows pharmacological properties similar to those of the previously described 5-oxo-ETE receptor expressed on eosinophils, neutrophils, and monocytes. These cell types show chemotactic responses to 5-oxo-ETE, and this eicosanoid has been proposed to play a key role in the inflammatory response. The molecular identification of a receptor binding 5-oxo-ETE will expand our understanding of the physiological role of this mediator and may provide new therapeutic opportunities.