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.

Phenotype-based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis

“…Cysteinyl leukotrienes are proinflammatory agents that increase vascular permeability (26,29) through receptor-mediated activation of phospholipase C, phosphoinositide-3-kinase, and/or extracellular signal-related kinases (29,67,68). This increased permeability can increase extravasation of proangiogenic factors that can remodel the extracellular environment and promote growth of new vessels.…”

The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery

“…This raises interesting possibilities for what could activate ChemR23 and makes future experiments that study release of endogenous chemerin critical. Not only chemerin, but lipids such as resolvin E1, can activate ChemR23 (2).…”

Recognition of Bacterial Signal Peptides by Mammalian Formyl Peptide Receptors

“…Although FPRs have been named according to their capability to detect formylated peptides (5,17), these receptors can recognize structurally diverse agonists with no obvious common pattern in amino acid sequence or natural origin (3,16). Such ligands include N-formylated, C-amidated, and unmodified peptides from bacterial and viral pathogens as well as host-endogenous mitochondrial peptides and several nonpeptide agonists, such as resolvin D1 and lipoxin A4 (3,5,18). FPRs detect a wide range of structurally diverse pro-and antiinflammatory ligands associated with important human diseases, such as amyloidosis, Alzheimer disease, HIV, and inflammatory pain (19,20).…”