Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7

Abstract

The endogenous ligands for the LT, lipoxin (LX) and oxoeicosanoid receptors are bioactive products produced by the action of the lipoxygenase family of enzymes. The LT receptors BLT1 and BLT2 , are activated by LTB4 and the CysLT1 and CysLT2 receptors are activated by the cysteinyl-LTs, whereas oxoeicosanoids exert their action through the OXE receptor. In contrast to these pro-inflammatory mediators, LXA4 transduces responses associated with the resolution of inflammation through the receptor FPR2/ALX (ALX/FPR2). The aim of the present review is to give a state of the field on these receptors, with focus on recent important findings. For example, BLT1 receptor signalling in cancer and the dual role of the BLT2 receptor in pro- and anti-inflammatory actions have added more complexity to lipid mediator signalling. Furthermore, a cross-talk between the CysLT and P2Y receptor systems has been described, and also the presence of novel receptors for cysteinyl-LTs, such as GPR17 and GPR99. Finally, lipoxygenase metabolites derived from ω-3 essential polyunsaturated acids, the resolvins, activate the receptors GPR32 and ChemR23. In conclusion, the receptors for the lipoxygenase products make up a sophisticated and tightly controlled system of endogenous pro- and anti-inflammatory signalling in physiology and pathology.

Keywords: LTs; cancer; cardiovascular; eicosanoids; inflammation; lipoxins; lipoxygenase; oxoeicosanoids; respiratory.

Figure 1

Members of the LT receptor family are depicted in yellow, whereas shaded rectangles indicate related receptors, for which formal ligand pairing is yet to be agreed. ETE, eicosatetraenoic acid; FLAP, 5-lipoxygenase activating protein; GPR, G protein-coupled receptor; HETE, hydroxyeicosatetraenoic acid; HpETE, hydroperoxyeicosatetraenoic acid; LO, lipoxygenase; LTC₄S, LT C₄ synthase; LTA₄H, LTA₄ hydrolase; LX, lipoxin.