Human CYSLTR2

Leukotriene receptors

The leukotriene receptors are activated by the endogenous ligands leukotrienes (LT), synthesized from lipoxygenase metabolism of arachidonic acid. The human BLT₁ receptor is the high affinity LTB₄ receptor whereas the... [read more] BLT₂ receptor in addition to being a low-affinity LTB₄ receptor also binds several other lipoxygenase-products, such as 12S-HETE, 12S-HPETE, 15S-HETE, and the thromboxane synthase product 12-hydroxyheptadecatrienoic acid. The BLT receptors mediate chemotaxis and immunomodulation in several leukocyte populations and are in addition expressed on non-myeloid cells, such as vascular smooth muscle and endothelial cells. In addition to BLT receptors, LTB₄ has been reported to bind to the peroxisome proliferator activated receptor (PPAR) α [1] and the vanilloid TRPV1 ligand-gated nonselective cation channel [2]. The receptors for the cysteinyl-leukotrienes (i.e. LTC₄, LTD₄ and LTE₄) are termed CysLT₁ and CysLT₂ and exhibit distinct expression patterns in human tissues, mediating for example smooth muscle cell contraction, regulation of vascular permeability, and leukocyte activation. There is also evidence in the literature for additional CysLT receptor subtypes, derived from functional in vitro studies, radioligand binding and in mice lacking both CysLT₁ and CysLT₂ receptors [3]. Cysteinyl-leukotrienes have also been suggested to signal through the P2Y₁₂ receptor [4,5,6], GPR17 [7] and GPR99 [8].

References

1. Lin Q, Ruuska SE, Shaw NS, et al. Ligand selectivity of the peroxisome proliferator-activated receptor alpha. Biochemistry 1999;38:185-90.
2. McHugh D, McMaster RS, Pertwee RG, et al. Novel compounds that interact with both leukotriene B4 receptors and vanilloid TRPV1 receptors. J Pharmacol Exp Ther 2006;316:955-65.
3. Bäck M, Powell WS, Dahlén SE, et al. Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7. Br J Pharmacol 2014;171:3551-74.
4. Fredman G, Van Dyke TE, Serhan CN. Resolvin E1 regulates adenosine diphosphate activation of human platelets. Arterioscler Thromb Vasc Biol 2010;30:2005-13.
5. Nonaka Y, Hiramoto T, Fujita N. Identification of endogenous surrogate ligands for human P2Y12 receptors by in silico and in vitro methods. Biochem Biophys Res Commun 2005;337:281-288.
6. Paruchuri S, Tashimo H, Feng C, et al. Leukotriene E4-induced pulmonary inflammation is mediated by the P2Y12 receptor. J Exp Med 2009;206:2543-55.
7. Ciana P, Fumagalli M, Trincavelli ML, et al. The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor. EMBO J 2006;25:4615-27.
8. Kanaoka Y, Maekawa A, Austen KF. Identification of GPR99 protein as a potential third cysteinyl leukotriene receptor with a preference for leukotriene E4 ligand. J Biol Chem 2013;288:10967-72.

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