Identification of a G Protein-Coupled Receptor for 5-oxo-Eicosatetraenoic Acid

Abstract

5-Oxo-eicosatetraenoic acid (5-oxo-ETE), a metabolite of arachidonic acid, is known to act as a chemoattractant for neutrophils and eosinophils and is thought to be involved in inflammation and allergy. We have screened novel G protein-coupled receptors (GPCRs) from the human genome sequence by computational search (Takeda et al. FEBS Lett., 52097-520101 (2002)), and identified a GPCR (hGPCR48) among them as a receptor for 5-oxo-ETE. The fusion protein of hGPCR48 with G protein α i1 subunit was found to be activated by 5-oxo-ETE, 5(S)-hydroperoxy-eicosatetraenoic acid (5(S)-HPETE), and arachidonic acid with EC 5 0 of 5.5 nM, 19 nM, and 1.4 μM, respectively, as was assessed by agonist-stimulated [ 3 5 S]GTPγS binding activity. This EC 5 0 value for 5-oxo-ETE was essentially the same as the reported values for its binding to plasma membranes of neutrophils and for its effect to induce the increase of the intracellular Ca 2 + ions and the chemotaxis of neutrophils and eosinophils. The expression of hGPCR48 in neutrophils was evidenced by RT-PCR. These results indicate that hGPCR48 is a receptor for 5-oxo-ETE that is responsible for 5-oxo-ETE-induced chemotaxis of neutrophils. In addition, hGPCR48 might exert other physiological functions, because RT-PCR indicated its expression in liver and kidney at high levels and in the central nervous system at low levels.