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.