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CysLT2 receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 270

Nomenclature: CysLT2 receptor

Family: Leukotriene receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 346 13q14.2 CYSLTR2 cysteinyl leukotriene receptor 2 19,36
Mouse 7 309 14 D3 Cysltr2 cysteinyl leukotriene receptor 2 23,37
Rat 7 309 15p11 Cysltr2 cysteinyl leukotriene receptor 2
Previous and Unofficial Names Click here for help
LTC4 | CYSLT2R | HG57
Database Links Click here for help
Specialist databases
GPCRdb cltr2_human (Hs), cltr2_mouse (Mm), cltr2_rat (Rn)
Other databases
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human cysteinyl leukotriene receptor 2 in complex with ONO-2570366 (C2221 space group).
PDB Id:  6RZ6
Ligand:  ONO-2570366
Resolution:  2.43Å
Species:  Human
References:  17
Natural/Endogenous Ligands Click here for help
LTC4
LTD4
LTE4
Comments: LTC4 and LTD4 are more potent agonists than LTE4
Potency order of endogenous ligands
LTC4LTD4 >> LTE4  [19,36,49]

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]LTC4 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 7.0 – 10.8 pKd 7-8,49
pKd 10.5 (Kd 2.9x10-11 M) in HUVEC [8]
pKd 7.0 – 10.8 (1.07x10-7 – 1.58x10-11 M) Kd1 and Kd2 in human lung parenchyma [7]
pKd 8.5 (Kd 3x10-9 M) in COS-1 cells [49]
[3H]LTD4 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 7.3 – 9.4 pKd 19
pKd 7.3 – 9.4 (Kd 5.01x10-8 – 3.98x10-10 M) Kd1 and Kd-2 in COS-7 cells [19]
LTD4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.3 – 8.1 pKi 7
pKi 7.3 – 8.1 Ki1 and Ki2 against [3H]LTC4 in human lung parenchyma [7]
LTE4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist 6.5 pKi 7
pKi 6.5 Ki against [3H]LTC4 in human lung parenchyma [7]
LTC4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 7.0 – 8.6 pEC50 8,19,36,49,56
pEC50 8.1 – 8.6 (EC50 8.9x10-9 – 2.3x10-9 M) Ca2+ mobilisation assay in HEK-293 cells [36,49]
pEC50 7.3 (EC50 5.4x10-8 M) β-arrestin assay in C2C12 myofibroblasts [56]
pEC50 7.2 (EC50 5.7x10-8 M) Ca2+ mobilization assay in HUVEC [8]
pEC50 7.0 – 7.2 (EC50 9.4x10-8 – 5.8x10-8 M) aequorin-based Ca2+ assay in HEK-293 cells [19,56]
LTD4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.8 – 8.6 pEC50 8,19,36,49,56
pEC50 8.0 – 8.6 (EC50 9.3x10-9 – 2.5x10-9 M) Ca2+ mobolisation assay in HEK-293 cells [8,36,49]
pEC50 7.5 (EC50 3.5x10-8 M) β-arrestin assay in C2C12 [56]
pEC50 7.4 (EC50 3.6x10-8 M) Ca2+ mobilization assay in HUVEC [8]
pEC50 6.8 – 7.0 (EC50 1.44x10-7 – 1.04x10-7 M) aequorin-based Ca2+ assay in HEK-293 cells [19,56]
N-methyl LTC4 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.9 – 8.1 pEC50 56
pEC50 8.1 (EC50 8.7x10-9 M) β-arrestin assay in C2C12 myofibroblasts [56]
pEC50 6.9 (EC50 1.22x10-7 M) aequorin-based Ca2+ assay in HEK-293 cells [56]
BAYu9773 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Partial agonist 7.0 – 7.2 pEC50 36,55
pEC50 7.2 (EC50 6.9x10-8 M) aequorin-based Ca2+ assay in CHO cells [55]
pEC50 7.0 (EC50 9.2x10-8 M) Ca2+ mobilization assay in HEK-293 cells [36]
LTE4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist 5.6 – 7.1 pEC50 19,36,49,56
pEC50 6.5 – 7.1 (EC50 2.93x10-7 – 7.7x10-8 M) Ca2+ mobilization assay in HEK-293 cells [36,49]
pEC50 5.6 – 5.9 (EC50 2.3x10-6 – 1.208x10-6 M) aequorin-based Ca2+ assay in HEK-293 cells [19,56]
LTC4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 8.4 – 8.5 pIC50 19,36
pIC50 8.4 – 8.5 (IC50 4x10-9 – 3.3x10-9 M) against [3H]LTD4 in COS-7 or HEK-293 cells [19,36]
LTD4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.2 – 8.1 pIC50 36,49
pIC50 8.1 (IC50 7x10-9 M) against [3H]LTD4 in HEK-293 cells [36]
pIC50 7.2 (IC50 5.9x10-8 M) against [3H]LTC4 in COS-1 cells [49]
BAYu9773 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Partial agonist 6.2 – 6.4 pIC50 19,36,55
pIC50 6.2 – 6.4 (IC50 5.97x10-7 – 4x10-7 M) against [3H]LTD4 COS-7, HEK-293 or CHO cells [19,36,55]
LTE4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist 5.7 – 6.2 pIC50 19,36,49
pIC50 6.2 – 6.2 (IC50 7x10-7 – 6.93x10-7 M) against [3H]LTD4 in COS-7 or HEK-293 cells [19,36]
pIC50 5.7 (IC50 1.89x10-6 M) against [3H]LTC4 in COS-1 cells [49]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BayCysLT2 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 – 8.4 pA2 8
pA2 8.4 [8]
Description: against LTC4 and LTD4 Ca2+ mobilisation assays in HUVEC
pA2 8.3 [8]
Description: against LTD4 Ca2+ mobilisation assay in COS-7 cells
BAYu9773 Small molecule or natural product Immunopharmacology Ligand Rn Antagonist 6.8 – 7.7 pA2 52
pA2 6.8 – 7.7 [52]
Description: against LTC4 and LTD4 induced contraction in smooth muscle preparation
pranlukast Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 7.1 pA2 6
pA2 7.1 [6]
Description: against LTC4 Ca2+ mobilization assay in HUVEC
zafirlukast Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 6.9 pA2 6
pA2 6.9 against LTC4 Ca2+ mobilisation assay in HUVEC [6]
iralukast Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.8 pA2 6
pA2 6.8 against LTC4 Ca2+ mobilisation assay in HUVEC [6]
pobilukast Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pA2 6
pA2 6.2 [6]
Description: against LTC4 Ca2+ mobilisation assay in HUVEC
BAYu9773 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.5 – 6.7 pKB 27
pKB 6.5 – 6.7 against LTD4 and LTC4 human pulmonary vein contraction [27]
[3H]ICI-198615 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 5.2 pKd 44
pKd 5.2 in human lung parenchyma [44]
compound 15b [PMID: 31811124] Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.2 pIC50 17
pIC50 9.2 (IC50 6.2x10-10 M) [17]
Description: Determined by measuring inhibition of LTD4-induced IP1 production by the antagonist.
HAMI3379 Small molecule or natural product Hs Antagonist 7.4 – 8.4 pIC50 55
pIC50 8.4 – 8.4 (IC50 4.4x10-9 – 3.8x10-9 M) against 10nM LTD4 -LTC4 aequorin-based Ca2+ assay in CHO cells [55]
pIC50 7.4 (IC50 3.8x10-8 M) [55]
Description: against [3H]LTD4 in CHO cells
ONO-2570366 Small molecule or natural product Ligand has a PDB structure Hs Antagonist 7.8 pIC50 17
pIC50 7.8 (IC50 1.4x10-8 M) [17]
Description: Determined by measuring inhibition of LTD4-induced IP1 production by antagonists.
BayCysLT2 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.6 – 7.3 pIC50 35
pIC50 6.6 – 7.3 (IC50 2.74x10-7 – 5.3x10-8 M) [35]
Description: against 30-300nM LTD4 arrestin assay in C2C12 myofibroblasts
BAYu9773 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 5.3 – 7.7 pIC50 35-36,55
pIC50 7.7 – 7.7 (IC50 1.9x10-8 – 1.8x10-8 M) against 10nM LTD4 - LTC4 aequorin-based Ca2+ assay in CHO cells [55]
pIC50 6.5 (IC50 3x10-7 M) against 10nM LTD4 Ca2+ mobilisation assay in HEK-293 [36]
pIC50 5.3 (IC50 4.6x10-6 M) against 300nM LTD4 β-arrestin Assay in C2C12 myofibroblasts [35]
compound 13e [PMID: 31811124] Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.7 pIC50 17
pIC50 5.7 (IC50 1.8x10-6 M) [17]
Description: Determined by measuring inhibition of LTD4-induced IP1 production by the antagonist.
pranlukast Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 5.4 pIC50 19
pIC50 5.4 (IC50 3.62x10-6 M) [19]
Description: against [3H]LTD4 in COS-7 cells
zafirlukast Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 5.1 – 5.2 pIC50 19,55
pIC50 5.2 (IC50 7x10-6 M) against 10nM LTD4 aequorin-based Ca2+ assay in CHO cells [55]
pIC50 5.1 (IC50 7.397x10-6 M) againist [3H]LTD4 in COS-7 cells [19]
View species-specific antagonist tables
Antagonist Comments
Montelukast and MK-571 are totally inactive at this receptor [8,19,36,49].
Immunopharmacology Comments
CysLT2 is a receptor for cysteinyl-leukotrienes. Both CysLT2 and CysLT1 mediate cysteinyl-leukotriene-induced modulation of smooth muscle cell contraction, regulation of vascular permeability, and leukocyte activation.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  8,19
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Other - See Comments
Comments:  p38 activation
References:  33
Tissue Distribution Click here for help
Monocyte derived dendritic cells
Species:  Human
Technique:  RT-PCR and FACS analyses
References:  11
Human umbilical vein endothelial cells
Species:  Human
Technique:  RT-PCR and immunocytochemistry
References:  28,34,48
Human platelets
Species:  Human
Technique:  RT-PCR and Western blotting
References:  18
Conjunctival goblet cells
Species:  Human
Technique:  Immunohistochemistry and Western blotting
References:  12
Eosinophils, monocytes; neutrophils and T lymphocytes (weaker espression)
Species:  Human
Technique:  RT-PCR
References:  28,34
Heart, adrenals, peripheral blood leukocytes, placenta, spleen, lymph nodes, brain (strong expression); kidney, ovary, prostate and testis (weak expression)
Species:  Human
Technique:  Northern blot
References:  19,49
Lung interstitial macrophages and smooth muscle cells (weaker espression); peripherial blood monocytes and eosinophils; chromaffincontaining adrenal medulla cells; Purkinje cells
Species:  Human
Technique:  in situ hybridisation
References:  19
Heart (ventricles, atria, septum and apex), adrenals, placenta, peripheral blood leukocytes, spleen and lymph nodes; pituatiry and spinal cord (weaker espression)
Species:  Human
Technique:  Microarray analysis
References:  36
Hart (atria, left ventricle, pericardium) and coronary artery smooth muscle cells
Species:  Human
Technique:  RT-PCR
References:  25
Myocytes, fibroblasts, and vascular smooth muscle cells
Species:  Human
Technique:  in situ hybridisation
References:  25
Human umbilical vein endothelial cells
Species:  Human
Technique:  Western Blot and immunocytochemistry
References:  8
Saphenous veins
Species:  Human
Technique:  RT-PCR
References:  32
Glands and epithelium of nasal mucosa
Species:  Human
Technique:  Immunohistochemistry
References:  10
Eosinophils, mast cells and mononuclear cells (in nasal lavage from patients with allergic rhinitis)
Species:  Human
Technique:  in situ hybridisation and immunocytochemistry
References:  14
Nasal polyps from aspirin hypersensitive patients
Species:  Human
Technique:  Immunocytochemistry
References:  1
Nasal mucosa (patients with allergic rhinitis)
Species:  Human
Technique:  Western blot, immunohistochemistry
References:  47
Basophils
Species:  Human
Technique:  RT-PCR
References:  16
Smooth muscle cells of cerebral arteries and veins
Species:  Human
Technique:  Immunohistochemistry
References:  20
Colorectal cancer tissue
Species:  Human
Technique:  Immunohistochemistry
References:  29-30
Neuronal of colonic myenteric plexus
Species:  Mouse
Technique:  Loss-of-function model
References:  3
Functional Assays Click here for help
Measurement of Ca2+ mobilization in cell endogenously expressing the CysLT2 receptor
Species:  Human
Tissue:  Coronary smooth muscle cells
Response measured:  [Ca2+]i increase
References:  25
Measurement of Ca2+ mobilization in cells transfected with the human CysLT2 receptor
Species:  Human
Tissue:  HEK-293 or COS-7 cells
Response measured:  [Ca2+]i increase
References:  8,19,36,49,56
Measurement of Ca2+ mobilization in cell endogenously expressing the CysLT2 receptor
Species:  Human
Tissue:  Umbilical vein endothelial cells
Response measured:  [Ca2+]i increase
References:  8,28,48
Measurement of aquaporin 4 upregulation in cell endogenously expressing the CysLT2 receptor
Species:  Rat
Tissue:  Astrocytes
Response measured:  Aquaporin 4 upregulation
References:  43
Measurement of aquaporin 4 upregulation in cell endogenously expressing the CysLT2 receptor
Species:  Mouse
Tissue:  Brain
Response measured:  Aquaporin 4 upregulation
References:  54
β-galactosidase complementation assay for β-Arrestin binding in cell transfected with the human CysLT2 receptor
Species:  Human
Tissue:  C2C12 myofibroblasts
Response measured:  β-Arrestin binding to the CysLT2 receptor
References:  56
Measurement of p38 activation and IL-8 production in cell endogenously expressing the CysLT2 receptor
Species:  Human
Tissue:  Mast and umbilical vein endothelial cells
Response measured:  Increased IL-8 secretion
References:  33,50
Physiological Functions Click here for help
PAF accumulation and neutrophil adhesion
Species:  Human
Tissue:  Endothelial cells
References:  31
Secretion of von Willebrand factor and of P-selectin expression
Species:  Human
Tissue:  Umbilical vein endothelial cells
References:  13,41
Up-regulation of early inducible genes
Species:  Human
Tissue:  Umbilical vein endothelial cells
References:  53
Myosin light-chain kinase activation, stress fiber formation and cell contraction
Species:  Human
Tissue:  Umbilical vein endothelial cells
References: 
Edema
Species:  Rat
Tissue:  Brain
References: 
Edema
Species:  Mouse
Tissue:  Brain
References:  54
Cell death
Species:  Rat
Tissue:  PC12 cells and astrocytes
References:  21,45
Contraction
Species:  Human
Tissue:  Smooth muscle of pulmonary veins
References:  27
Endothelium-mediated indirect relaxation
Species:  Human
Tissue:  Pulmonary arteries and veins
References:  38
Physiological Consequences of Altering Gene Expression Click here for help
Endothelial cell-specific human CysLT2R transgenic mouse model. Increased vascular permeability and systemic pressor response.
Species:  Mouse
Tissue:  Endothelial cells
Technique:  Gene overexpression
References:  22
Attenuation of bleomycin-induced pulmonary inflammation and fibrosis; reduced vascular permeability associated with IgE-dependent passive cutaneous anaphylaxis
Species:  Mouse
Tissue:  Lung
Technique:  Gene knockouts
References:  5
In a oxygen-induced retinopathy model enhanced vasoobliteration-vasoproliferation and retinal edema
Species:  Mouse
Tissue:  Retina
Technique:  Gene knockouts
References:  2
Increased eosinophilic pulmonary inflammation, serum IgE, and Th2 cytokines
Species:  Mouse
Tissue:  Lung
Technique:  Gene knockouts
References:  4
Reduced skin thickening and collagen deposition in ovalbumin-sensitized skin
Species:  Mouse
Tissue:  Skin
Technique:  Gene knockouts
References:  39
Endothelial cell-specific human CysLT2R transgenic mouse mode. Phenotype: aggrevation of myocardial ischemia-reperfusion injury
Species:  Mouse
Tissue:  Endothelial cells
Technique:  Gene overexpression
References:  24
Decreased colitis disease progression via a reduction in inflammation-associated tissue edema and increased neuronal sensitivity to nociceptive stimuli
Species:  Mouse
Tissue:  Intestine
Technique:  Gene knockouts
References:  3
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cysltr2tm1Ykn Cysltr2tm1Ykn/Cysltr2tm1Ykn
C57BL/6-Cysltr2
MGI:1917336  MP:0009811 abnormal prostaglandin level PMID: 15328359 
Cysltr2tm1Sish Cysltr2tm1Sish/Cysltr2tm1Sish
involves: C57BL/6
MGI:1917336  MP:0000343 altered response to myocardial infarction PMID: 18276782 
Cysltr2tm1Ykn Cysltr2tm1Ykn/Cysltr2tm1Ykn
C57BL/6-Cysltr2
MGI:1917336  MP:0005597 decreased susceptibility to type I hypersensitivity reaction PMID: 15328359 
Cysltr2tm1Ykn Cysltr2tm1Ykn/Cysltr2tm1Ykn
C57BL/6-Cysltr2
MGI:1917336  MP:0006050 pulmonary fibrosis PMID: 15328359 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Asthma, susceptibility to
Disease Ontology: DOID:2841
OMIM: 600807
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human M201V c.601A>G rs41347648 42,51
Disease:  Uveal melanoma
Description: Uveal melanoma is the most common eye cancer in adults. It is distinct from skin melanomas.
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human L129Q Encodes a highly biased, constitutively active mutant receptor that acts as an oncogenic driver for uveal melanoma 9
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Polymorphism associated with atopic asthma in the Japanese population.
Nucleotide change:  c.-1220A>C
References:  15
Type:  Single nucleotide polymorphisms
Species:  Human
Description:  Increased response to montelukast associated with the SNPs rs912277 and rs912278
SNP accession: 
References:  26
Type:  Single nucleotide polymorphisms
Species:  Human
Description:  Polymorphism associated with aspirin intolerance in asthmatics
Nucleotide change:  c.-819T>G, c.2078C>T, c.2534A>G, c.2545+297A>G
References:  40,46

References

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1. Adamusiak AM, Stasikowska-Kanicka O, Lewandowska-Polak A, Danilewicz M, Wagrowska-Danilewicz M, Jankowski A, Kowalski ML, Pawliczak R. (2012) Expression of arachidonate metabolism enzymes and receptors in nasal polyps of aspirin-hypersensitive asthmatics. Int Arch Allergy Immunol, 157 (4): 354-62. [PMID:22123288]

2. Barajas-Espinosa A, Ni NC, Yan D, Zarini S, Murphy RC, Funk CD. (2012) The cysteinyl leukotriene 2 receptor mediates retinal edema and pathological neovascularization in a murine model of oxygen-induced retinopathy. FASEB J, 26 (3): 1100-9. [PMID:22131271]

3. Barajas-Espinosa A, Ochoa-Cortes F, Moos MP, Ramirez FD, Vanner SJ, Funk CD. (2011) Characterization of the cysteinyl leukotriene 2 receptor in novel expression sites of the gastrointestinal tract. Am J Pathol, 178 (6): 2682-9. [PMID:21641390]

4. Barrett NA, Fernandez JM, Maekawa A, Xing W, Li L, Parsons MW, Austen KF, Kanaoka Y. (2012) Cysteinyl leukotriene 2 receptor on dendritic cells negatively regulates ligand-dependent allergic pulmonary inflammation. J Immunol, 189 (9): 4556-65. [PMID:23002438]

5. Beller TC, Maekawa A, Friend DS, Austen KF, Kanaoka Y. (2004) Targeted gene disruption reveals the role of the cysteinyl leukotriene 2 receptor in increased vascular permeability and in bleomycin-induced pulmonary fibrosis in mice. J Biol Chem, 279 (44): 46129-34. [PMID:15328359]

6. Capra V, Carnini C, Accomazzo MR, Di Gennaro A, Fiumicelli M, Borroni E, Brivio I, Buccellati C, Mangano P, Carnevali S et al.. (2015) Autocrine activity of cysteinyl leukotrienes in human vascular endothelial cells: Signaling through the CysLT₂ receptor. Prostaglandins Other Lipid Mediat, 120: 115-25. [PMID:25839425]

7. Capra V, Nicosia S, Ragnini D, Mezzetti M, Keppler D, Rovati GE. (1998) Identification and characterization of two cysteinyl-leukotriene high affinity binding sites with receptor characteristics in human lung parenchyma. Mol Pharmacol, 53 (4): 750-8. [PMID:9547367]

8. Carnini C, Accomazzo MR, Borroni E, Vitellaro-Zuccarello L, Durand T, Folco G, Rovati GE, Capra V, Sala A. (2011) Synthesis of cysteinyl leukotrienes in human endothelial cells: subcellular localization and autocrine signaling through the CysLT2 receptor. FASEB J, 25 (10): 3519-28. [PMID:21753081]

9. Ceraudo E, Horioka M, Mattheisen JM, Hitchman TD, Moore AR, Kazmi MA, Chi P, Chen Y, Sakmar TP, Huber T. (2021) Direct evidence that the GPCR CysLTR2 mutant causative of uveal melanoma is constitutively active with highly biased signaling. J Biol Chem, 296: 100163. [PMID:33288675]

10. Corrigan C, Mallett K, Ying S, Roberts D, Parikh A, Scadding G, Lee T. (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]

11. Dannull J, Schneider T, Lee WT, de Rosa N, Tyler DS, Pruitt SK. (2012) Leukotriene C4 induces migration of human monocyte-derived dendritic cells without loss of immunostimulatory function. Blood, 119 (13): 3113-22. [PMID:22323449]

12. Dartt DA, Hodges RR, Li D, Shatos MA, Lashkari K, Serhan CN. (2011) Conjunctival goblet cell secretion stimulated by leukotrienes is reduced by resolvins D1 and E1 to promote resolution of inflammation. J Immunol, 186 (7): 4455-66. [PMID:21357260]

13. Datta YH, Romano M, Jacobson BC, Golan DE, Serhan CN, Ewenstein BM. (1995) Peptido-leukotrienes are potent agonists of von Willebrand factor secretion and P-selectin surface expression in human umbilical vein endothelial cells. Circulation, 92 (11): 3304-11. [PMID:7586318]

14. Figueroa DJ, Borish L, Baramki D, Philip G, Austin CP, Evans JF. (2003) Expression of cysteinyl leukotriene synthetic and signalling proteins in inflammatory cells in active seasonal allergic rhinitis. Clin Exp Allergy, 33 (10): 1380-8. [PMID:14519144]

15. Fukai H, Ogasawara Y, Migita O, Koga M, Ichikawa K, Shibasaki M, Arinami T, Noguchi E. (2004) Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13q14 and atopic asthma. Pharmacogenetics, 14 (10): 683-90. [PMID:15454733]

16. Gauvreau GM, Plitt JR, Baatjes A, MacGlashan DW. (2005) Expression of functional cysteinyl leukotriene receptors by human basophils. J Allergy Clin Immunol, 116 (1): 80-7. [PMID:15990778]

17. Gusach A, Luginina A, Marin E, Brouillette RL, Besserer-Offroy É, Longpré JM, Ishchenko A, Popov P, Patel N, Fujimoto T et al.. (2019) Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors. Nat Commun, 10 (1): 5573. DOI: 10.1038/s41467-019-13348-2 [PMID:31811124]

18. Hasegawa S, Ichiyama T, Hashimoto K, Suzuki Y, Hirano R, Fukano R, Furukawa S. (2010) Functional expression of cysteinyl leukotriene receptors on human platelets. Platelets, 21 (4): 253-9. [PMID:20433311]

19. Heise CE, O'Dowd BF, Figueroa DJ, Sawyer N, Nguyen T, Im DS, Stocco R, Bellefeuille JN, Abramovitz M, Cheng R et al.. (2000) Characterization of the human cysteinyl leukotriene 2 receptor. J Biol Chem, 275 (39): 30531-6. [PMID:10851239]

20. Hu H, Chen G, Zhang JM, Zhang WP, Zhang L, Ge QF, Yao HT, Ding W, Chen Z, Wei EQ. (2005) Distribution of cysteinyl leukotriene receptor 2 in human traumatic brain injury and brain tumors. Acta Pharmacol Sin, 26 (6): 685-90. [PMID:15916734]

21. Huang XJ, Zhang WP, Li CT, Shi WZ, Fang SH, Lu YB, Chen Z, Wei EQ. (2008) Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation. Glia, 56 (1): 27-37. [PMID:17910051]

22. Hui Y, Cheng Y, Smalera I, Jian W, Goldhahn L, Fitzgerald GA, Funk CD. (2004) Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressure. Circulation, 110 (21): 3360-6. [PMID:15545522]

23. Hui Y, Yang G, Galczenski H, Figueroa DJ, Austin CP, Copeland NG, Gilbert DJ, Jenkins NA, Funk CD. (2001) The murine cysteinyl leukotriene 2 (CysLT2) receptor. cDNA and genomic cloning, alternative splicing, and in vitro characterization. J Biol Chem, 276 (50): 47489-95. [PMID:11591709]

24. Jiang W, Hall SR, Moos MP, Cao RY, Ishii S, Ogunyankin KO, Melo LG, Funk CD. (2008) Endothelial cysteinyl leukotriene 2 receptor expression mediates myocardial ischemia-reperfusion injury. Am J Pathol, 172 (3): 592-602. [PMID:18276782]

25. Kamohara M, Takasaki J, Matsumoto M, Matsumoto Si, Saito T, Soga T, Matsushime H, Furuichi K. (2001) Functional characterization of cysteinyl leukotriene CysLT(2) receptor on human coronary artery smooth muscle cells. Biochem Biophys Res Commun, 287 (5): 1088-92. [PMID:11587533]

26. Klotsman M, York TP, Pillai SG, Vargas-Irwin C, Sharma SS, van den Oord EJ, Anderson WH. (2007) Pharmacogenetics of the 5-lipoxygenase biosynthetic pathway and variable clinical response to montelukast. Pharmacogenet Genomics, 17 (3): 189-96. [PMID:17460547]

27. Labat C, Ortiz JL, Norel X, Gorenne I, Verley J, Abram TS, Cuthbert NJ, Tudhope SR, Norman P, Gardiner P et al.. (1992) A second cysteinyl leukotriene receptor in human lung. J Pharmacol Exp Ther, 263 (2): 800-5. [PMID:1331415]

28. Lötzer K, Spanbroek R, Hildner M, Urbach A, Heller R, Bretschneider E, Galczenski H, Evans JF, Habenicht AJ. (2003) Differential leukotriene receptor expression and calcium responses in endothelial cells and macrophages indicate 5-lipoxygenase-dependent circuits of inflammation and atherogenesis. Arterioscler Thromb Vasc Biol, 23 (8): e32-6. [PMID:12816882]

29. Magnusson C, Ehrnström R, Olsen J, Sjölander A. (2007) An increased expression of cysteinyl leukotriene 2 receptor in colorectal adenocarcinomas correlates with high differentiation. Cancer Res, 67 (19): 9190-8. [PMID:17909024]

30. Magnusson C, Mezhybovska M, Lörinc E, Fernebro E, Nilbert M, Sjölander A. (2010) Low expression of CysLT1R and high expression of CysLT2R mediate good prognosis in colorectal cancer. Eur J Cancer, 46 (4): 826-35. [PMID:20064706]

31. McIntyre TM, Zimmerman GA, Prescott SM. (1986) Leukotrienes C4 and D4 stimulate human endothelial cells to synthesize platelet-activating factor and bind neutrophils. Proc Natl Acad Sci USA, 83 (7): 2204-8. [PMID:3457383]

32. Mechiche H, Candenas L, Pinto FM, Nazeyrollas P, Clément C, Devillier P. (2004) Characterization of cysteinyl leukotriene receptors on human saphenous veins: antagonist activity of montelukast and its metabolites. J Cardiovasc Pharmacol, 43 (1): 113-20. [PMID:14668576]

33. Mellor EA, Frank N, Soler D, Hodge MR, Lora JM, Austen KF, Boyce JA. (2003) Expression of the type 2 receptor for cysteinyl leukotrienes (CysLT2R) by human mast cells: Functional distinction from CysLT1R. Proc Natl Acad Sci USA, 100 (20): 11589-93. [PMID:13679572]

34. Mita H, Hasegawa M, Saito H, Akiyama K. (2001) 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. [PMID:11696047]

35. Ni NC, Yan D, Ballantyne LL, Barajas-Espinosa A, St Amand T, Pratt DA, Funk CD. (2011) A selective cysteinyl leukotriene receptor 2 antagonist blocks myocardial ischemia/reperfusion injury and vascular permeability in mice. J Pharmacol Exp Ther, 339 (3): 768-78. [PMID:21903747]

36. Nothacker HP, Wang Z, Zhu Y, Reinscheid RK, Lin SH, Civelli O. (2000) 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]

37. Ogasawara H, Ishii S, Yokomizo T, Kakinuma T, Komine M, Tamaki K, Shimizu T, Izumi T. (2002) Characterization of mouse cysteinyl leukotriene receptors mCysLT1 and mCysLT2: differential pharmacological properties and tissue distribution. J Biol Chem, 277 (21): 18763-8. [PMID:11854273]

38. Ortiz JL, Gorenne I, Cortijo J, Seller A, Labat C, Sarria B, Abram TS, Gardiner PJ, Morcillo E, Brink C. (1995) Leukotriene receptors on human pulmonary vascular endothelium. Br J Pharmacol, 115 (8): 1382-6. [PMID:8564195]

39. Oyoshi MK, He R, Kanaoka Y, ElKhal A, Kawamoto S, Lewis CN, Austen KF, Geha RS. (2012) Eosinophil-derived leukotriene C4 signals via type 2 cysteinyl leukotriene receptor to promote skin fibrosis in a mouse model of atopic dermatitis. Proc Natl Acad Sci USA, 109 (13): 4992-7. [PMID:22416124]

40. Park JS, Chang HS, Park CS, Lee JH, Lee YM, Choi JH, Park HS, Kim LH, Park BL, Choi YH et al.. (2005) Association analysis of cysteinyl-leukotriene receptor 2 (CYSLTR2) polymorphisms with aspirin intolerance in asthmatics. Pharmacogenet Genomics, 15 (7): 483-92. [PMID:15970796]

41. Pedersen KE, Bochner BS, Undem BJ. (1997) Cysteinyl leukotrienes induce P-selectin expression in human endothelial cells via a non-CysLT1 receptor-mediated mechanism. J Pharmacol Exp Ther, 281 (2): 655-62. [PMID:9152370]

42. Pillai SG, Cousens DJ, Barnes AA, Buckley PT, Chiano MN, Hosking LK, Cameron LA, Fling ME, Foley JJ, Green A et al.. (2004) A coding polymorphism in the CYSLT2 receptor with reduced affinity to LTD4 is associated with asthma. Pharmacogenetics, 14 (9): 627-33. [PMID:15475736]

43. Qi LL, Fang SH, Shi WZ, Huang XQ, Zhang XY, Lu YB, Zhang WP, Wei EQ. (2011) CysLT2 receptor-mediated AQP4 up-regulation is involved in ischemic-like injury through activation of ERK and p38 MAPK in rat astrocytes. Life Sci, 88 (1-2): 50-6. [PMID:21055410]

44. Rovati GE, Giovanazzi S, Mezzetti M, Nicosia S. (1992) Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma. Biochem Pharmacol, 44 (7): 1411-5. [PMID:1329767]

45. Sheng WW, Li CT, Zhang WP, Yuan YM, Hu H, Fang SH, Zhang L, Wei EQ. (2006) Distinct roles of CysLT1 and CysLT2 receptors in oxygen glucose deprivation-induced PC12 cell death. Biochem Biophys Res Commun, 346 (1): 19-25. [PMID:16756959]

46. Shin JA, Chang HS, Park SM, Jang AS, Park SW, Park JS, Uh ST, Il Lim G, Rhim T, Kim MK et al.. (2009) Genetic effect of CysLTR2 polymorphisms on its mRNA synthesis and stabilization. BMC Med Genet, 10: 106. [PMID:19840403]

47. Shirasaki H, Kanaizumi E, Seki N, Fujita M, Kikuchi M, Himi T. (2013) Localization and up-regulation of cysteinyl leukotriene-2 receptor in human allergic nasal mucosa. Allergol Int, 62 (2): 223-8. [PMID:23524649]

48. Sjöström M, Johansson AS, Schröder O, Qiu H, Palmblad J, Haeggström JZ. (2003) 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]

49. Takasaki J, Kamohara M, Matsumoto M, Saito T, Sugimoto T, Ohishi T, Ishii H, Ota T, Nishikawa T, Kawai Y et al.. (2000) The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor. Biochem Biophys Res Commun, 274 (2): 316-22. [PMID:10913337]

50. Thompson C, Cloutier A, Bossé Y, Poisson C, Larivée P, McDonald PP, Stankova J, Rola-Pleszczynski M. (2008) Signaling by the cysteinyl-leukotriene receptor 2. Involvement in chemokine gene transcription. J Biol Chem, 283 (4): 1974-84. [PMID:18048362]

51. Thompson MD, Storm van's Gravesande K, Galczenski H, Burnham WM, Siminovitch KA, Zamel N, Slutsky A, Drazen JM, George SR, Evans JF et al.. (2003) A cysteinyl leukotriene 2 receptor variant is associated with atopy in the population of Tristan da Cunha. Pharmacogenetics, 13 (10): 641-9. [PMID:14515063]

52. Tudhope SR, Cuthbert NJ, Abram TS, Jennings MA, Maxey RJ, Thompson AM, Norman P, Gardiner PJ. (1994) BAYu9773, a novel antagonist of cysteinyl-leukotrienes with activity against two receptor subtypes. Eur J Pharmacol, 264: 317-323. [PMID:7698171]

53. Uzonyi B, Lötzer K, Jahn S, Kramer C, Hildner M, Bretschneider E, Radke D, Beer M, Vollandt R, Evans JF 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 USA, 103 (16): 6326-31. [PMID:16606835]

54. Wang ML, Huang XJ, Fang SH, Yuan YM, Zhang WP, Lu YB, Ding Q, Wei EQ. (2006) Leukotriene D4 induces brain edema and enhances CysLT2 receptor-mediated aquaporin 4 expression. Biochem Biophys Res Commun, 350 (2): 399-404. [PMID:17010308]

55. Wunder F, Tinel H, Kast R, Geerts A, Becker EM, Kolkhof P, Hütter J, Ergüden J, Härter M. (2010) Pharmacological characterization of the first potent and selective antagonist at the cysteinyl leukotriene 2 (CysLT(2)) receptor. Br J Pharmacol, 160 (2): 399-409. [PMID:20423349]

56. Yan D, Stocco R, Sawyer N, Nesheim ME, Abramovitz M, Funk CD. (2011) Differential signaling of cysteinyl leukotrienes and a novel cysteinyl leukotriene receptor 2 (CysLT₂) agonist, N-methyl-leukotriene C₄, in calcium reporter and β arrestin assays. Mol Pharmacol, 79 (2): 270-8. [PMID:21078884]

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