Leukotriene receptors (nomenclature agreed by NC-IUPHAR subcommittee on Leukotriene and Lipoxin Receptors, [4]) are activated by the endogenous ligands leukotriene B₄ (LTB₄), LTC₄, LTD₄, LTE₄, 12R-HETE and 12S-HETE. CysLT₁ and CysLT₂ are co-expressed by most myeloid cells. However, the function of CysLT₂ remains unclear. CysLT₂ has been demonstrated to exert a suppressive influence on CysLT₁ expression, suggesting an autoregulatory function which is indicated by a reported up-regulation of CysLT-mediated responses in mice lacking CysLT₂ receptors [18].

Leukotrienes bind extensively to enzymes in their metabolic pathways (glutathione-S-transferase/LTC₄ synthase, γ-glutamyltranspeptidase and several aminopeptidases) and can also bind to peroxisome proliferator-activated receptor α (PPARα, [22]) and the FPR2/ALX lipoxin receptor [10], complicating the interpretation of radioligand binding and functional studies (e.g. LTC₄ is rapidly converted in many systems to LTD₄). Metabolic inhibitors (e.g. serine–borate complex) reduce this problem but can also have nonspecific effects.

BAYu9773 is an antagonist at CysLT₁ (6.8–7.7) and a reduced efficacy agonist at CysLT₂ receptors. The CysLT₁ and CyLT₂ receptors also respond to uracil nucleotides [25-26]. GPR17 has been described as a ‘dualistic’ receptor responding to both uracil nucleotides and cysteinyl leukotrienes, responses which may be inhibited by antagonists of either P2 or CysLT receptors [6].

Lipoxin A4 receptors (FPR2/ALX, nomenclature agreed by NC-IUPHAR on Leukotriene and Lipoxin Receptors; [40]) are activated by the endogenous lipid-derived, anti-inflammatory ligands lipoxin A₄ (LXA₄) and 15-epi-LXA₄ (aspirin triggered lipoxin A4, ATL). The FPR2/ALX receptor also interacts with endogenous peptide and protein ligands, such as MHC binding peptide [5] as well as annexin I (ANXA1) and its N-terminal peptides [31]. In addition, a soluble hydrolytic product of protease action on the urokinase-type plasminogen activator receptor has been reported to activate the FPR2/ALX receptor [32]. Furthermore, FPR2/ALX has been suggested to act as a receptor mediating proinflammatory actions of the acute-phase reactant, serum amyloid A [36-37].

Oxoeicosanoid receptors (OXE, nomenclature agreed by NC-IUPHAR on Oxoeicosanoid Receptors; [3]) are activated by endogenous chemotactic eicosanoid ligands oxidised at the C-5 position, with 5-oxo-ETE the most potent agonist identified for this receptor.

Note that the data for FPR2/ALX are also reproduced on the Formylpeptide receptor pages. A receptor selective for LXB₄ has been suggested from functional studies [1,24,33]. Initial characterization of the heterologously expressed OXE receptor suggested that polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and EPA, acted as receptor antagonists [15].

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