International Union of Pharmacology XLIV. Nomenclature for the Oxoeicosanoid Receptor CHARLES BRINK, SVEN-ERIK DAHL ´ EN, JEFFREY DRAZEN, JILLY F. EVANS, DOUGLAS W. P. HAY, G. ENRICO ROVATI, CHARLES N. SERHAN, TAKAO SHIMIZU, AND TAKEHIKO YOKOMIZO Centre National de la Recherche Scientifique UMR 7131, Ho ˆpital Broussais, Ba ˆ timent Les Mariniers, Paris, France (C.B.); Unit for Experimental Asthma and Allergy, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (S.-E.D); Harvard Medical School, Brigham and Woman’s Hospital, Boston, Massachussetts (J.M.D.); Department of Pharmacology, Merck & Co., West Point, Pennsylvania (J.F.E.); GlaxoSmithKline, King of Prussia, Pennsylvania (D.W.P.H.); Division of Molecular Pharmacology, Pharmacological Sciences, Milan, Italy (G.E.R.); Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia Research Laboratory, Brigham and Woman’s Hospital/Harvard Medical School, Boston, Massachusetts (C.N.S.); and Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, Bunkyo-Ko, Tokyo, Japan (T.S., T.Y.) Abstract ............................................................................... 149 I. Overview .............................................................................. 149 II. Introduction ............................................................................ 150 III. Biosynthesis of oxoeicosanoids ........................................................... 150 A. Cofactors for oxoeicosanoid formation .................................................. 151 B. Cellular production of oxoeicoanoids ................................................... 152 IV. Nomenclature for oxoeicosanoid receptors ................................................. 152 V. Molecular characteristics of oxoeicosanoid receptors ........................................ 153 VI. Significance of oxoeicosanoid receptors .................................................... 154 VII. Conclusion ............................................................................. 156 References ............................................................................. 156 Abstract——Oxoeicosanoids are a family of biologi- cally active arachidonic acid derivatives that have been intimately linked with cellular migration. These metab- olites are not only potent chemotaxins but also elicit oxygen radical production as well as induce secretory events in different cells. The most potent native ligand reported is 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo- ETE), and the cell membrane receptor activated has now been cloned. This receptor is distinct from those re- ceptors activated by either the prostaglandins or the leukotrienes. The purpose of this review is to briefly summarize the molecular evidence and highlight the significance of this receptor. In addition, an official no- menclature for this oxoeicosanoid receptor is proposed. I. Overview The biological responses provoked by arachidonic acid have generally been attributed to the conversion of this substrate to a variety of metabolites. The enzymatic oxidation of arachidonic acid leads to the formation of a family of lipid mediators known as eicosanoids. These products are produced in a well controlled fashion under the direction of specific enzymes (Fig. 1). Modifications in the levels of the metabolites of arachidonic acid have been intimately linked not only with a variety of cellular functions but also with inflammation and disease. In an attempt to understand this modification, one research approach was to isolate and inhibit the enzymes respon- sible for the formation of specific metabolites. Other investigations were undertaken to characterize and identify the receptors that were activated by the various arachidonic acid products. These efforts have lead to a considerable clarification of the mediator effects and have provided compounds with therapeutic value for patients. Address correspondence to: Charles Brink, Researcher (CNRS CR- 1), CNRS UMR 7131, Ho ˆpital Broussais, Ba ˆ timent Les Mariniers, 96, rue Didot, 75014 Paris, France. E-mail: charlesbrink@hotmail.com Article, publication date, and citation information can be found at http://pharmrev.aspetjournals.org. DOI: 10.1124/pr.56.1.4. 1 Abbreviations: 5-LO, 5-lipoxygenase; 5-oxo-ETE, 5-oxo-6,8,11,14-eico- satetraenoic acid; 5-HpETE, 5(S)-hydroperoxy-6,8,11,14-eicosatetraenoic acid; 5-HETE, 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid; LT, leukotri- ene; 5-oxo-15-HETE, 5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid; PMN, polymorphonuclear neutrophil; ECL, eosinophil chemotactic lipid; OXE, oxoeicosanoid; HEK, human embryonic kidney; GPCR, G-protein- coupled receptor; TNF, tumor necrosis factor ; PAF, platelet-activating factor; CysLT, cysteinyl-leukotriene; GM-CSF, granulocyte macrophage- colony-stimulating factor; [ 35 S]GTPS, guanosine 5'-O-(3-[ 35 S]thio)triphos- phate; IUPHAR, International Union of Pharmacology. 0031-6997/04/5601-149 –157$7.00 PHARMACOLOGICAL REVIEWS Vol. 56, No. 1 Copyright © 2004 by The American Society for Pharmacology and Experimental Therapeutics 40402/1135362 Pharmacol Rev 56:149–157, 2004 Printed in U.S.A 149 at Kyushu Univ (M080) Central Library on March 23, 2012 pharmrev.aspetjournals.org Downloaded from