Cysteinyl leukotriene receptor 2
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Cysteinyl leukotriene receptor 2, also termed CYSLTR2, is a receptor for cysteinyl leukotrienes (LT) (see
Gene
The human CysLTR2 gene maps to the long arm of chromosome 13 at position 13q14, a chromosomal region that has long been linked to asthma and other allergic diseases.
Receptor
CySLTR2
CysLTR2, similar to CysLTR1, is a
In addition to CysLTR1,
Other studies on model cells for allergy have defined
CysLTR2 inhibitors
There are as yet no selective inhibitors of CysLTR2 that are in clinical use (see Clinical significance section below). However, Gemilukast (ONO-6950) reportedly inhibits both CysLTR1 and CysLTR2. The drug is currently being evaluated in phase II trials for the treatment of asthma.[17]
CysLTR2 polymorphism
Polymorphism in the CysLTR2 gene resulting in a single amino acid substitution, M201V (i.e. amino acid methionine changed for valine at the 201 position of CysLTR2 protein) has been negatively associated in Transmission disequilibrium testing with the inheritance of asthma in separate populations of: a) white and African-Americans from 359 families with a high prevalence of asthma in Denmark and Minnesota, USA, and b) 384 families with a high prevalence of asthma from the Genetics of Asthma International Network. The M201V CysLTR2 variant exhibits decreased responsiveness to LTD4 suggesting that this hypo-responsiveness underlies its asthma transmission-protecting effect.[18][19] A -1220A>C (i.e. nucleotide adenine substituted for cytosine at position 1220 upstream from the transcription start site) gene polymorphism variant in intron III the upstream region of CysLTR2 has been associated significantly with development of asthma in a Japanese population; the impact of this polymorphism on the genes expression or product has not been determined.[9] These results suggest that CYSLTR2 contributes to the etiology and development asthma and that drugs targeting CYSLTR2 may work in a manner that differs from those of CYSLTR1 antagonists.[9]
Clinical significance
The CysLT-induced activation of CysLTR2 induces many of the same in vitro responses of cells involved in allergic reactions as well as the in vivo allergic responses in animal models as that induced by CysLT-induced CysLTR1 (see
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000152207 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033470 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 10913337.
- S2CID 7097419.
- ^ "Entrez Gene: CYSLTR2 cysteinyl leukotriene receptor 2".
- S2CID 27541608.
- ^ PMID 15454733.
- ^ S2CID 11433313.
- ^ PMID 25572555.
- S2CID 23133928.
- S2CID 206159450.
- ^ PMID 24991451.
- PMID 27185938.
- PMID 23504326.
- PMID 26200813.
- S2CID 14676388.
- ^ "WikiGenes - Collaborative Publishing".
- PMID 21936577.
- PMID 24313690.
- S2CID 31311115.
- PMID 26678823.
- PMID 19647860.
- PMID 17693579.
Further reading
- Nothacker HP, Wang Z, Zhu Y, et al. (2001). "Molecular cloning and characterization of a second human cysteinyl leukotriene receptor: discovery of a subtype selective agonist". Mol. Pharmacol. 58 (6): 1601–8. PMID 11093801.
- Mita H, Hasegawa M, Saito H, Akiyama K (2002). "Levels of cysteinyl leukotriene receptor mRNA in human peripheral leucocytes: significantly higher expression of cysteinyl leukotriene receptor 2 mRNA in eosinophils". Clin. Exp. Allergy. 31 (11): 1714–23. S2CID 43278015.
- Takeda S, Kadowaki S, Haga T, et al. (2002). "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Lett. 520 (1–3): 97–101. PMID 12044878.
- Shirasaki H, Kanaizumi E, Watanabe K, et al. (2003). "Expression and localization of the cysteinyl leukotriene 1 receptor in human nasal mucosa". Clin. Exp. Allergy. 32 (7): 1007–12. S2CID 25871662.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMID 12477932.
- Sjöström M, Johansson AS, Schröder O, et al. (2004). "Dominant expression of the CysLT2 receptor accounts for calcium signaling by cysteinyl leukotrienes in human umbilical vein endothelial cells". Arterioscler. Thromb. Vasc. Biol. 23 (8): e37–41. PMID 12816881.
- Mellor EA, Frank N, Soler D, et al. (2003). "Expression of the type 2 receptor for cysteinyl leukotrienes (CysLT2R) by human mast cells: Functional distinction from CysLT1R". Proc. Natl. Acad. Sci. U.S.A. 100 (20): 11589–93. PMID 13679572.
- Thompson MD, Storm van's Gravesande K, Galczenski H, et al. (2004). "A cysteinyl leukotriene 2 receptor variant is associated with atopy in the population of Tristan da Cunha". Pharmacogenetics. 13 (10): 641–9. PMID 14515063.
- Dunham A, Matthews LH, Burton J, et al. (2004). "The DNA sequence and analysis of human chromosome 13". Nature. 428 (6982): 522–8. PMID 15057823.
- Fukai H, Ogasawara Y, Migita O, et al. (2005). "Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13q14 and atopic asthma". Pharmacogenetics. 14 (10): 683–90. PMID 15454733.
- Pillai SG, Cousens DJ, Barnes AA, et al. (2005). "A coding polymorphism in the CYSLT2 receptor with reduced affinity to LTD4 is associated with asthma". Pharmacogenetics. 14 (9): 627–33. PMID 15475736.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. PMID 15489334.
- Hui Y, Cheng Y, Smalera I, et al. (2005). "Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressure". Circulation. 110 (21): 3360–6. PMID 15545522.
- Corrigan C, Mallett K, Ying S, et al. (2005). "Expression of the cysteinyl leukotriene receptors cysLT(1) and cysLT(2) in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis". J. Allergy Clin. Immunol. 115 (2): 316–22. PMID 15696087.
- Uzonyi B, Lötzer K, Jahn S, et al. (2006). "Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate strongly correlated early genes in human endothelial cells". Proc. Natl. Acad. Sci. U.S.A. 103 (16): 6326–31. PMID 16606835.
- Woszczek G, Chen LY, Nagineni S, et al. (2007). "IFN-gamma induces cysteinyl leukotriene receptor 2 expression and enhances the responsiveness of human endothelial cells to cysteinyl leukotrienes". J. Immunol. 178 (8): 5262–70. PMID 17404310.
- Klotsman M, York TP, Pillai SG, et al. (2007). "Pharmacogenetics of the 5-lipoxygenase biosynthetic pathway and variable clinical response to montelukast". Pharmacogenet. Genomics. 17 (3): 189–96. S2CID 6275533.
External links
- "Leukotriene Receptors: CysLT2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 3 March 2016. Retrieved 5 December 2008.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.