CysLT<sub>1</sub> receptor | Leukotriene receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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CysLT1 receptor

target has curated data in GtoImmuPdb

Target id: 269

Nomenclature: CysLT1 receptor

Family: Leukotriene receptors

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 337 Xq13.2-21.1 CYSLTR1 cysteinyl leukotriene receptor 1 42,78
Mouse 7 352 X D Cysltr1 cysteinyl leukotriene receptor 1
Rat 7 339 Xq31 Cysltr1 cysteinyl leukotriene receptor 1
Previous and Unofficial Names
HG55 | LTD4 | CYSLT1R | leukotriene D4 receptor
Database Links
Specialist databases
GPCRDB cltr1_human (Hs), cltr1_mouse (Mm), cltr1_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of cysteinyl leukotriene receptor 1 in complex with pranlukast.
PDB Id:  6RZ4
Ligand:  pranlukast
Resolution:  2.7Å
Species:  Human
Natural/Endogenous Ligands
Comments: LTD4 is the most potent endogenous agonist
Potency order of endogenous ligands
LTD4 > LTC4 > LTE4  [42,78]

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]LTD4 Hs Full agonist 8.2 – 10.6 pKd 10-13,42
pKd 8.6 – 10.6 Kd1 and Kd2 in human lung parenchyma [11-12]
pKd 9.3 (Kd 5x10-10 M) in U937 cells [10]
pKd 8.2 – 10.2 Kd1 and Kd2 in COS-7 cells [13,42]
LTC4 Hs Full agonist 7.0 – 8.1 pKi 12
pKi 7.0 – 8.1 Ki1 and Ki2 against [3H]LTD4 in human lung parenchyma [12]
LTE4 Hs Partial agonist 7.1 – 7.8 pKi 12
pKi 7.1 – 7.8 Ki against [3H]LTD4 in human lung parenchyma [12]
LTD4 Hs Full agonist 7.3 – 9.4 pEC50 10,15,42,58,78,85,87
pEC50 9.4 (EC50 4x10-10 M) pigment dispersion in X. laevis melanophores [42]
pEC50 8.5 (EC50 3x10-9 M) Ca2+ activated chloride conductance in X. laevis oocytes [42]
pEC50 8.5 (EC50 3.4x10-9 M) Ca2+ mobilisation assay in U937 cells [10]
pEC50 7.3 – 9.2 (EC50 4.6x10-8 – 6x10-10 M) Ca2+ mobilisation assay in COS-7 or HEK-293 cells [15,42,58,78,85,87]
LTC4 Hs Full agonist 7.4 – 7.7 pEC50 42,58,78,85
pEC50 7.7 (EC50 2.1x10-8 M) pigment dispersion in X. laevis melanophores [42]
pEC50 7.4 – 7.7 (EC50 4.3x10-8 – 2x10-8 M) Ca2+ mobilisation assay in COS-7 or HEK-293 cells [58,78,85]
LTE4 Hs Partial agonist 6.4 – 7.2 pEC50 42,58,78,85,95
pEC50 6.6 – 7.2 (EC50 2.4x10-7 – 5.8x10-8 M) Ca2+ mobilisation assay in COS-7 or HEK-293 cells [58,78,85]
pEC50 6.7 (EC50 2.12x10-7 M) pigment dispersion in X. laevis melanophores [42]
pEC50 6.4 (EC50 3.91x10-7 M) aequorin-based Ca2+ assay in HEK-293 cells [95]
N-methyl LTC4 Hs Partial agonist 5.7 pEC50 95
pEC50 5.7 (EC50 2x10-6 M) aequorin-based Ca2+ assay in HEK-293 cells [95]
LTD4 Hs Full agonist 8.1 pIC50 78
pIC50 8.1 (IC50 9x10-9 M) against [3H]LTD4 in HEK-293 cells [78]
LTE4 Hs Partial agonist 6.6 – 7.0 pIC50 42
pIC50 6.6 – 7.0 (IC50 2.74x10-7 – 1.07x10-7 M) against [3H]LTD4 in COS-7 cells [42]
LTC4 Hs Full agonist 6.4 – 6.5 pIC50 42
pIC50 6.4 – 6.5 (IC50 3.6x10-7 – 3.46x10-7 M) against [3H]LTD4 in COS-7 cells [42]
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
triple modulator 10 [PMID: 29878767] Hs Antagonist 8.7 pA2 80
pA2 8.7 [80]
BayCysLT2 Hs Antagonist 6.4 pA2 15
pA2 6.4 against LTD4 Ca2+ mobilisation assay in COS-7 cells [15]
[3H]ICI-198615 Hs Antagonist 10.6 pKd 75
pKd 10.6 (Kd 2.5x10-11 M) [75]
Description: in human lung parenchyma
ICI198615 Cp Antagonist 9.7 pKi 28
pKi 9.7 (Ki 2x10-10 M) [28]
zafirlukast Hs Antagonist 8.9 pKi 11,73
pKi 8.9 zafirlukast is only about 100-fold selective for CysLT1 [11,73]
Description: against [3H]LTD4 in human lung parenchyma
SR2640 Hs Antagonist 8.7 pKi
pKi 8.7
montelukast Hs Antagonist 8.6 pKi 73
pKi 8.6 [73]
Description: against [3H]LTD4 in human lung parenchyma
sulukast Hs Antagonist 8.3 pKi
pKi 8.3
pranlukast Hs Antagonist 7.1 – 8.8 pKi 11,73
pKi 7.1 – 8.8 [11,73]
Description: against [3H]LTD4 in human lung parenchyma
iralukast Hs Antagonist 7.8 pKi 11
pKi 7.8 against [3H]LTD4 in human lung parenchyma [11]
pobilukast Hs Antagonist 7.1 pKi 12
pKi 7.1 [12]
Description: against [3H]LTD4 in human lung parenchyma
pranlukast Hs Antagonist 8.1 – 10.0 pIC50 42,78
pIC50 10.0 (IC50 1x10-10 M) against 33nM LTD4 Ca2+ mobilization assay in HEK-293 [78]
pIC50 8.1 – 8.4 (IC50 7.2x10-9 – 4.3x10-9 M) against [3H]LTD4 in COS-7 or HEK-293 cells [42,78]
compound 13e [PMID: 31811124] Hs Antagonist >9.0 pIC50 30
pIC50 >9.0 (IC50 <1x10-9 M) [30]
Description: Determined by measuring inhibition of LTD4-induced IP1 production by the antagonist.
zafirlukast Hs Antagonist 7.7 – 9.6 pIC50 42,78,94
pIC50 9.6 (IC50 2.6x10-10 M) against 33nM LTD4 Ca2+ mobilization assay in HEK-293 [78]
pIC50 8.6 – 8.7 (IC50 2.6x10-9 – 1.8x10-9 M) [42,78]
Description: against [3H]LTD4 in COS-7 or HEK-293 cells
pIC50 7.7 (IC50 2x10-8 M) against 10nM LTD4 aequorin-based Ca2+ assay in CHO cells [94]
montelukast Hs Antagonist 8.3 – 8.6 pIC50 42,78
pIC50 8.6 (IC50 2.3x10-9 M) against 33nM LTD4 Ca2+ mobilization assay in HEK-293 [78]
pIC50 8.3 – 8.6 (IC50 4.9x10-9 – 2.3x10-9 M) [42,78]
Description: against [3H]LTD4 in COS-7 or HEK-293 cells
verlukast Hs Antagonist 8.0 – 8.1 pIC50 39
pIC50 8.1 (IC50 8x10-9 M) [39]
Description: against [3H]LTD4 in human lung homogenate
pIC50 8.0 (IC50 1.07x10-8 M) [39]
Description: Antagonism of [3H]leukotriene D4 binding in dimethyl sulfoxide differentiated U937 cell membrane preparations.
MK-571 Hs Antagonist 8.0 pIC50 42
pIC50 8.0 (IC50 1x10-8 M) [42]
Description: Antagonism of [3H]LTD4 binding in COS-7 cells.
pobilukast Hs Antagonist 7.5 – 8.3 pIC50 78
pIC50 8.3 (IC50 5.5x10-9 M) against 33nM LTD4 Ca2+ mobilization assay in HEK-293 [78]
pIC50 7.5 (IC50 3x10-8 M) against [3H]LTD4 in HEK-293 [78]
compound 15b [PMID: 31811124] Hs Antagonist 6.9 pIC50 30
pIC50 6.9 (IC50 1.2x10-7 M) [30]
Description: Determined by measuring inhibition of LTD4-induced IP1 production by the antagonist.
BAYu9773 Hs Antagonist 5.3 – 6.4 pIC50 58,94
pIC50 6.4 (IC50 4.4x10-7 M) against 10nM LTD4 Ca2+ mobilization assay in HEK-293 [58]
pIC50 5.3 (IC50 5x10-6 M) against 10nM LTD4 aequorin-based Ca2+ assay in CHO cells [94]
View species-specific antagonist tables
Immunopharmacology Comments
CysLT1 is a receptor for cysteinyl-leukotrienes. Both CysLT1 and CysLT2 mediate cysteinyl-leukotriene-induced modulation of smooth muscle cell contraction, regulation of vascular permeability, and leukocyte activation.

Selective inhibition of CysLT1 receptor blocks the pro-inflammatory responses associated with allergic disorders that are mediated by this receptor. This pharmacological approach has been used for treating asthma and associated diseases for a considerable period of time, with several CysLT1-selective antagonists in clinical use.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes, IEA only
GO:0006954 inflammatory response IDA
click arrow to show/hide IEA associations
GO:0002437 inflammatory response to antigenic stimulus IEA
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  PI turnover and Ca2+ mobilisation. A number of different groups have reported a Gq/G11-dependent Ca2+ mobilization in monocytic leukemia U937 [10,68,92] or THP-1 cells [16,33], mast cells [54] or monocyte-derived macrophages [43]
References:  42,78
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Phospholipase C stimulation
Comments:  Other different cellular responses have been reported to be Gi/G0 coupled [2,4,14,21,33,38,63,65,74,76,79,82,93].
References:  10,68,81
Tissue Distribution
Small intestines and colon
Species:  Human
References:  42,78
Bronchiole smooth muscle, lung macrophages
Species:  Human
Technique:  In situ hybridisation, RT-PCR
References:  42
Peripheral blood leukocytes, spleen, lung, bronchus, small intestine and placenta
Species:  Human
Technique:  Northern blot
References:  42,78
Colorectal carcinoma cells
Species:  Human
References:  59
Human saphenous vein
Species:  Human
Technique:  RT-PCR
References:  51
Blood-derived monocytes/macrophages and U937 cells
Species:  Human
Technique:  RT-PCR
References:  13,43
Mast cells
Species:  Human
Technique:  RT-PCR and FACS
References:  54
Species:  Human
Technique:  RT-PCR, Western blot and FACS
References:  31
Airway mucosa
Species:  Human
References:  97
Species:  Human
Technique:  Immunohistochemistry
References:  25
Nasal polyps
Species:  Human
References:  17,72
Coronary artery smooth muscle cells
Species:  Human
Technique:  RT-PCR and immunocytochemistry
References:  23
Aortic valves
Species:  Human
Technique:  RT-PCR
References:  57
Functional Assays
Activation of mitogen-activated protein kinase (MAPK)
Species:  Human
Tissue:  THP-1 and U937, intestinal epithelial, Caco-2, airway smooth muscle and mast cells, peripheral blood monocytes/macrophages and chronic lymphocytic leukemia cells
Response measured:  ERK phosphorylation
References:  14,21,32-33,38,62,65,74
Activation of mitogen-activated protein kinase (MAPK)
Species:  Rat
Tissue:  Astrocytes
Response measured:  ERK phosphorylation
References:  18
Activation of pigment dispersion transfected with the human CysLT1 receptor
Species:  Human
Tissue:  X. laevis melanophores
Response measured:  Pigment dispersion
References:  42
Ca2+-activated chloride conductance in oocytes injected with human CysLT1 receptor
Species:  Human
Tissue:  X. laevis oocyte
Response measured:  Cl current
References:  42
Measurement of Ca2+ mobilization in HEK293 or COS-7 cells transfected with the human CysLT1 receptor
Species:  Human
Tissue:  HEK293 - COS-7
Response measured:  [Ca2+]i increase
References:  15,42,58,78,85,87
Physiological Functions
Cell proliferation
Species:  Rat
Tissue:  Vascular smooth muscle cells and astrocytes
References:  18,34,69
Species:  Human
Tissue:  Bronchi
References:  1,3,19-20,29,40,83,91
Cell proliferation
Species:  Human
Tissue:  Airway smooth muscle and epithelial cells, intestinal epithelial, Caco-2, eosinophil hematopoietic progenitor and mast cells, fibrocytes, prostate cancer and chronic lymphocytic leukemia cells
References:  7-9,21,24,38,49,60,62,66-67,74,89
Chemotactic activity and migration
Species:  Human
Tissue:  THP-1, hematopoietic stem and airway smooth muscle cells, eosinophils,intestinal epithelial cells, monocytes/macrophages, Th2 and chronic lymphocytic leukemia cells
References:  4,21,26,33,61,63-64,90,93
Actin reorganization
Species:  Human
Tissue:  Bronchial smooth muscle and intestinal epithelial cells
References:  45,47,76
Release of inflammatory mediators and cytokines
Species:  Human
Tissue:  U937, THP-1 and dendritic cells, eosinophils, blood mononuclear cells, macrophages and monocytes, airway epithelial cells, platelets and fibroblast
References:  2,8,22,26-27,31-32,35-37,50,67,71,86
Cell adhesion
Species:  Human
Tissue:  U937, intestinal epithelial and Caco-2 cells, eosinophils, hematopoietic stem and progenitor cells, polymorphonuclear leukocytes
References:  7,41,46,48,52-53,70,82
Activation of transcription factors
Species:  Human
Tissue:  THP-1 and dendritic cells, eosinophils, epithelial cells, peripheral blood monocytes/macrophages
References:  6,32,70,84,86
Physiological Functions Comments
Some physiological functions in cells expressing both CysLT1 and CysLT2 (e.g. eosinophils chemotaxis and adhesion) have been attributed to CysLT1 on the base of antagonist effect [55-56,77,88] However, most leukotriene receptor antagonist, but montelukast and MK-571, are also active at the CysLT2 and, thus, preclude unambiguous identification.
Physiological Consequences of Altering Gene Expression
Transgenic mice overexpressing the human CysLT1R in SMCs via the α-actin promoter exhibit significantly enhanced allergen-induced airway hyperresponsiveness following LTD4 challenge.
Species:  Mouse
Tissue:  Lung
Technique:  Gene overexpression, hCysLT1R transgene injected embryos
References:  96
CysLT1 receptor knockout mice exhibit aggravated bleomycin-induced pulmonary inflammation.
Species:  Mouse
Tissue:  Lung
Technique:  Gene knockouts
References:  5
CysLT1 receptor knockout mice exhibit significantly suppressed plasma protein extravasation, but not neutrophil infiltration, after zymosan-induced peritonitis or IgE-mediated passive cutaneous anaphylaxis
Species:  Mouse
Technique:  Gene knockouts
References:  44
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cysltr1tm1Ykn Cysltr1tm1Ykn/Cysltr1tm1Ykn
involves: C57BL/6
MGI:1926218  MP:0005621 abnormal cell physiology PMID: 11932261 
Cysltr1tm1Ykn Cysltr1tm1Ykn/Cysltr1tm1Ykn
involves: C57BL/6
MGI:1926218  MP:0005597 decreased susceptibility to type I hypersensitivity reaction PMID: 11932261 
Cysltr1tm1Ykn Cysltr1tm1Ykn/Cysltr1tm1Ykn
involves: C57BL/6
MGI:1926218  MP:0003071 decreased vascular permeability PMID: 11932261 
Cysltr1tm1Ykn Cysltr1tm1Ykn/Cysltr1tm1Ykn
involves: C57BL/6
MGI:1926218  MP:0002405 respiratory system inflammation PMID: 14970333 
General Comments
LTE4 may be the only selective agonist as LTC4 and LTD4 also activate CysLT2 receptors. However, when Ca2+ mobilisation is studied in transfected cells, LTE4 is much less potent than LTD4.


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1. Adelroth E, Morris MM, Hargreave FE, O'Byrne PM. (1986) Airway responsiveness to leukotrienes C4 and D4 and to methacholine in patients with asthma and normal controls. N. Engl. J. Med., 315 (8): 480-4. [PMID:3526153]

2. Bandeira-Melo C, Hall JC, Penrose JF, Weller PF. (2002) Cysteinyl leukotrienes induce IL-4 release from cord blood-derived human eosinophils. J. Allergy Clin. Immunol., 109 (6): 975-9. [PMID:12063527]

3. Barnes NC, Piper PJ, Costello JF. (1984) Comparative effects of inhaled leukotriene C4, leukotriene D4, and histamine in normal human subjects. Thorax, 39 (7): 500-4. [PMID:6463929]

4. Bautz F, Denzlinger C, Kanz L, Möhle R. (2001) Chemotaxis and transendothelial migration of CD34(+) hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1. Blood, 97 (11): 3433-40. [PMID:11369634]

5. Beller TC, Friend DS, Maekawa A, Lam BK, Austen KF, Kanaoka Y. (2004) Cysteinyl leukotriene 1 receptor controls the severity of chronic pulmonary inflammation and fibrosis. Proc. Natl. Acad. Sci. U.S.A., 101 (9): 3047-52. [PMID:14970333]

6. Bengtsson AM, Massoumi R, Sjölander A. (2008) Leukotriene D(4) induces AP-1 but not NFkappaB signaling in intestinal epithelial cells. Prostaglandins Other Lipid Mediat., 85 (3-4): 100-6. [PMID:18083053]

7. Boehmler AM, Drost A, Jaggy L, Seitz G, Wiesner T, Denzlinger C, Kanz L, Möhle R. (2009) The CysLT1 ligand leukotriene D4 supports alpha4beta1- and alpha5beta1-mediated adhesion and proliferation of CD34+ hematopoietic progenitor cells. J. Immunol., 182 (11): 6789-98. [PMID:19454674]

8. Bossé Y, Thompson C, McMahon S, Dubois CM, Stankova J, Rola-Pleszczynski M. (2008) Leukotriene D4-induced, epithelial cell-derived transforming growth factor beta1 in human bronchial smooth muscle cell proliferation. Clin. Exp. Allergy, 38 (1): 113-21. [PMID:18028462]

9. Braccioni F, Dorman SC, O'byrne PM, Inman MD, Denburg JA, Parameswaran K, Baatjes AJ, Foley R, Gauvreau GM. (2002) The effect of cysteinyl leukotrienes on growth of eosinophil progenitors from peripheral blood and bone marrow of atopic subjects. J. Allergy Clin. Immunol., 110 (1): 96-101. [PMID:12110827]

10. Capra V, Accomazzo MR, Ravasi S, Parenti M, Macchia M, Nicosia S, Rovati GE. (2003) Involvement of prenylated proteins in calcium signaling induced by LTD4 in differentiated U937 cells. Prostaglandins Other Lipid Mediat., 71 (3-4): 235-51. [PMID:14518564]

11. Capra V, Bolla M, Belloni PA, Mezzetti M, Folco GC, Nicosia S, Rovati GE. (1998) Pharmacological characterization of the cysteinyl-leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro. Br. J. Pharmacol., 123 (3): 590-8. [PMID:9504401]

12. 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]

13. Capra V, Ravasi S, Accomazzo MR, Citro S, Grimoldi M, Abbracchio MP, Rovati GE. (2005) CysLT1 receptor is a target for extracellular nucleotide-induced heterologous desensitization: a possible feedback mechanism in inflammation. J. Cell. Sci., 118 (Pt 23): 5625-36. [PMID:16306225]

14. Capra V, Ravasi S, Accomazzo MR, Parenti M, Rovati GE. (2004) CysLT1 signal transduction in differentiated U937 cells involves the activation of the small GTP-binding protein Ras. Biochem. Pharmacol., 67 (8): 1569-77. [PMID:15041474]

15. 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]

16. Chan CC, Ecclestone P, Nicholson DW, Metters KM, Pon DJ, Rodger IW. (1994) Leukotriene D4-induced increases in cytosolic calcium in THP-1 cells: dependence on extracellular calcium and inhibition with selective leukotriene D4 receptor antagonists. J. Pharmacol. Exp. Ther., 269 (3): 891-6. [PMID:8014876]

17. Chao SS, Graham SM, Brown CL, Kline JN, Hussain I. (2006) Cysteinyl leukotriene 1 receptor expression in nasal polyps. Ann. Otol. Rhinol. Laryngol., 115 (5): 394-7. [PMID:16739673]

18. Ciccarelli R, D'Alimonte I, Santavenere C, D'Auro M, Ballerini P, Nargi E, Buccella S, Nicosia S, Folco G, Caciagli F et al.. (2004) Cysteinyl-leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys-LT1 receptors and mitogen-activated protein kinase pathway. Eur. J. Neurosci., 20 (6): 1514-24. [PMID:15355318]

19. Davidson AB, Lee TH, Scanlon PD, Solway J, McFadden Jr ER, Ingram Jr RH, Corey EJ, Austen KF, Drazen JM. (1987) Bronchoconstrictor effects of leukotriene E4 in normal and asthmatic subjects. Am. Rev. Respir. Dis., 135 (2): 333-7. [PMID:3028218]

20. Drazen JM, Austen KF, Lewis RA, Clark DA, Goto G, Marfat A, Corey EJ. (1980) Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc. Natl. Acad. Sci. U.S.A., 77 (7): 4354-8. [PMID:6933488]

21. Drost AC, Seitz G, Boehmler A, Funk M, Norz KP, Zipfel A, Xue X, Kanz L, Möhle R. (2012) The G protein-coupled receptor CysLT1 mediates chemokine-like effects and prolongs survival in chronic lymphocytic leukemia. Leuk. Lymphoma, 53 (4): 665-73. [PMID:21936770]

22. Eap R, Jacques E, Semlali A, Plante S, Chakir J. (2012) Cysteinyl leukotrienes regulate TGF-β(1) and collagen production by bronchial fibroblasts obtained from asthmatic subjects. Prostaglandins Leukot. Essent. Fatty Acids, 86 (3): 127-33. [PMID:22316690]

23. Eaton A, Nagy E, Pacault M, Fauconnier J, Bäck M. (2012) Cysteinyl leukotriene signaling through perinuclear CysLT(1) receptors on vascular smooth muscle cells transduces nuclear calcium signaling and alterations of gene expression. J. Mol. Med., 90 (10): 1223-31. [PMID:22527886]

24. Espinosa K, Bossé Y, Stankova J, Rola-Pleszczynski M. (2003) CysLT1 receptor upregulation by TGF-beta and IL-13 is associated with bronchial smooth muscle cell proliferation in response to LTD4. J. Allergy Clin. Immunol., 111 (5): 1032-40. [PMID:12743568]

25. Figueroa DJ, Breyer RM, Defoe SK, Kargman S, Daugherty BL, Waldburger K, Liu Q, Clements M, Zeng Z, O'Neill GP et al.. (2001) Expression of the cysteinyl leukotriene 1 receptor in normal human lung and peripheral blood leukocytes. Am. J. Respir. Crit. Care Med., 163 (1): 226-33. [PMID:11208650]

26. Fregonese L, Silvestri M, Sabatini F, Rossi GA. (2002) Cysteinyl leukotrienes induce human eosinophil locomotion and adhesion molecule expression via a CysLT1 receptor-mediated mechanism. Clin. Exp. Allergy, 32 (5): 745-50. [PMID:11994100]

27. Frieri M, Therattil J, Wang SF, Huang CY, Wang YC. (2003) Montelukast inhibits interleukin-5 mRNA expression and cysteinyl leukotriene production in ragweed and mite-stimulated peripheral blood mononuclear cells from patients with asthma. Allergy Asthma Proc, 24 (5): 359-66. [PMID:14619337]

28. Galemmo RA Jr, Johnson WH Jr, Learn KS, Lee TD, Huang FC, Campbell HF, Youssefyeh R, O'Rourke SV, Schuessler G, Sweeney DM et al.. (1990) The development of a novel series of (quinolin-2-ylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 3. Structural variation of the acidic side chain to give antagonists of enhanced potency. J Med Chem, 33 (10): 2828-41. [PMID:2170649]

29. Griffin M, Weiss JW, Leitch AG, McFadden Jr ER, Corey EJ, Austen KF, Drazen JM. (1983) Effects of leukotriene D on the airways in asthma. N. Engl. J. Med., 308 (8): 436-9. [PMID:6823253]

30. 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]

31. 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]

32. Hashimoto K, Ichiyama T, Hasegawa M, Hasegawa S, Matsubara T, Furukawa S. (2009) Cysteinyl leukotrienes induce monocyte chemoattractant protein-1 in human monocyte/macrophages via mitogen-activated protein kinase and nuclear factor-kappaB pathways. Int. Arch. Allergy Immunol., 149 (3): 275-82. [PMID:19218821]

33. Hoshino M, Izumi T, Shimizu T. (1998) Leukotriene D4 activates mitogen-activated protein kinase through a protein kinase Calpha-Raf-1-dependent pathway in human monocytic leukemia THP-1 cells. J. Biol. Chem., 273 (9): 4878-82. [PMID:9478929]

34. 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]

35. Ichiyama T, Hasegawa M, Hashimoto K, Matsushige T, Hirano R, Furukawa S. (2009) Cysteinyl leukotrienes induce macrophage inflammatory protein-1 in human monocytes/macrophages. Int. Arch. Allergy Immunol., 148 (2): 147-53. [PMID:18802359]

36. Ichiyama T, Hasegawa M, Ueno Y, Makata H, Matsubara T, Furukawa S. (2005) Cysteinyl leukotrienes induce monocyte chemoattractant protein 1 in human monocytes/macrophages. Clin. Exp. Allergy, 35 (9): 1214-9. [PMID:16164450]

37. Ichiyama T, Kajimoto M, Hasegawa M, Hashimoto K, Matsubara T, Furukawa S. (2007) Cysteinyl leukotrienes enhance tumour necrosis factor-alpha-induced matrix metalloproteinase-9 in human monocytes/macrophages. Clin. Exp. Allergy, 37 (4): 608-14. [PMID:17430359]

38. Jiang Y, Kanaoka Y, Feng C, Nocka K, Rao S, Boyce JA. (2006) Cutting edge: Interleukin 4-dependent mast cell proliferation requires autocrine/intracrine cysteinyl leukotriene-induced signaling. J. Immunol., 177 (5): 2755-9. [PMID:16920908]

39. Jones TR, Zamboni R, Belley M, Champion E, Charette L, Ford-Hutchinson AW, Gauthier JY, Leger S, Lord A, Masson P et al.. (1991) Pharmacology of the leukotriene antagonist verlukast: the (R)-enantiomer of MK-571. Can. J. Physiol. Pharmacol., 69 (12): 1847-54. [PMID:1666333]

40. Kern R, Smith LJ, Patterson R, Krell RD, Bernstein PR. (1986) Characterization of the airway response to inhaled leukotriene D4 in normal subjects. Am. Rev. Respir. Dis., 133 (6): 1127-32. [PMID:3521417]

41. Kushiya M, Saito K, Kikuchi I, Kobayashi T, Hagiwara K, Kanazawa M, Nagata M. (2006) Differential effects of salbutamol and montelukast on eosinophil adhesion and superoxide anion generation. Int. Arch. Allergy Immunol., 140 Suppl 1: 17-22. [PMID:16772722]

42. Lynch KR, O'Neill GP, Liu Q, Im DS, Sawyer N, Metters KM, Coulombe N, Abramovitz M, Figueroa DJ, Zeng Z et al.. (1999) Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature, 399 (6738): 789-93. [PMID:10391245]

43. 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]

44. Maekawa A, Austen KF, Kanaoka Y. (2002) Targeted gene disruption reveals the role of cysteinyl leukotriene 1 receptor in the enhanced vascular permeability of mice undergoing acute inflammatory responses. J. Biol. Chem., 277 (23): 20820-4. [PMID:11932261]

45. Massoumi R, Larsson C, Sjölander A. (2002) Leukotriene D(4) induces stress-fibre formation in intestinal epithelial cells via activation of RhoA and PKCdelta. J. Cell. Sci., 115 (Pt 17): 3509-15. [PMID:12154081]

46. Massoumi R, Nielsen CK, Azemovic D, Sjölander A. (2003) Leukotriene D4-induced adhesion of Caco-2 cells is mediated by prostaglandin E2 and upregulation of alpha2beta1-integrin. Exp. Cell Res., 289 (2): 342-51. [PMID:14499635]

47. Massoumi R, Sjölander A. (1998) The inflammatory mediator leukotriene D4 triggers a rapid reorganisation of the actin cytoskeleton in human intestinal epithelial cells. Eur. J. Cell Biol., 76 (3): 185-91. [PMID:9716265]

48. Massoumi R, Sjölander A. (2001) Leukotriene D(4) affects localisation of vinculin in intestinal epithelial cells via distinct tyrosine kinase and protein kinase C controlled events. J. Cell. Sci., 114 (Pt 10): 1925-34. [PMID:11329379]

49. Matsuyama M, Hayama T, Funao K, Kawahito Y, Sano H, Takemoto Y, Nakatani T, Yoshimura R. (2007) Overexpression of cysteinyl LT1 receptor in prostate cancer and CysLT1R antagonist inhibits prostate cancer cell growth through apoptosis. Oncol. Rep., 18 (1): 99-104. [PMID:17549353]

50. Mattern MR, Mong S, Mong SM, Bartus JO, Sarau HM, Clark MA, Foley JJ, Crooke ST. (1990) Transient activation of topoisomerase I in leukotriene D4 signal transduction in human cells. Biochem. J., 265 (1): 101-7. [PMID:2154178]

51. 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]

52. Meliton AY, Munoz NM, Leff AR. (2007) Blockade of avidity and focal clustering of beta 2-integrin by cysteinyl leukotriene antagonism attenuates eosinophil adhesion. J. Allergy Clin. Immunol., 120 (6): 1316-23. [PMID:17904626]

53. Meliton AY, Muñoz NM, Osan CM, Meliton LN, Leff AR. (2010) Leukotriene D4 activates {beta}2-integrin adhesion in human polymorphonuclear leukocytes. Eur. Respir. J., 35 (2): 402-9. [PMID:19679609]

54. Mellor EA, Maekawa A, Austen KF, Boyce JA. (2001) Cysteinyl leukotriene receptor 1 is also a pyrimidinergic receptor and is expressed by human mast cells. Proc. Natl. Acad. Sci. U.S.A., 98 (14): 7964-9. [PMID:11438743]

55. Nagata M, Saito K, Kikuchi I, Hagiwara K, Kanazawa M. (2005) Effect of the cysteinyl leukotriene antagonist pranlukast on transendothelial migration of eosinophils. Int. Arch. Allergy Immunol., 137 Suppl 1: 2-6. [PMID:15947477]

56. Nagata M, Saito K, Tsuchiya K, Sakamoto Y. (2002) Leukotriene D4 upregulates eosinophil adhesion via the cysteinyl leukotriene 1 receptor. J. Allergy Clin. Immunol., 109 (4): 676-80. [PMID:11941318]

57. Nagy E, Andersson DC, Caidahl K, Eriksson MJ, Eriksson P, Franco-Cereceda A, Hansson GK, Bäck M. (2011) Upregulation of the 5-lipoxygenase pathway in human aortic valves correlates with severity of stenosis and leads to leukotriene-induced effects on valvular myofibroblasts. Circulation, 123 (12): 1316-25. [PMID:21403093]

58. 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]

59. Ohd JF, Nielsen CK, Campbell J, Landberg G, Löfberg H, Sjölander A. (2003) Expression of the leukotriene D4 receptor CysLT1, COX-2, and other cell survival factors in colorectal adenocarcinomas. Gastroenterology, 124 (1): 57-70. [PMID:12512030]

60. Panettieri RA, Tan EM, Ciocca V, Luttmann MA, Leonard TB, Hay DW. (1998) Effects of LTD4 on human airway smooth muscle cell proliferation, matrix expression, and contraction In vitro: differential sensitivity to cysteinyl leukotriene receptor antagonists. Am. J. Respir. Cell Mol. Biol., 19 (3): 453-61. [PMID:9730873]

61. Parameswaran K, Cox G, Radford K, Janssen LJ, Sehmi R, O'Byrne PM. (2002) Cysteinyl leukotrienes promote human airway smooth muscle migration. Am. J. Respir. Crit. Care Med., 166 (5): 738-42. [PMID:12204874]

62. Parhamifar L, Jeppsson B, Sjölander A. (2005) Activation of cPLA2 is required for leukotriene D4-induced proliferation in colon cancer cells. Carcinogenesis, 26 (11): 1988-98. [PMID:15975962]

63. Parmentier CN, Fuerst E, McDonald J, Bowen H, Lee TH, Pease JE, Woszczek G, Cousins DJ. (2012) Human T(H)2 cells respond to cysteinyl leukotrienes through selective expression of cysteinyl leukotriene receptor 1. J. Allergy Clin. Immunol., 129 (4): 1136-42. [PMID:22391114]

64. Paruchuri S, Broom O, Dib K, Sjölander A. (2005) The pro-inflammatory mediator leukotriene D4 induces phosphatidylinositol 3-kinase and Rac-dependent migration of intestinal epithelial cells. J. Biol. Chem., 280 (14): 13538-44. [PMID:15657050]

65. Paruchuri S, Hallberg B, Juhas M, Larsson C, Sjölander A. (2002) Leukotriene D(4) activates MAPK through a Ras-independent but PKCepsilon-dependent pathway in intestinal epithelial cells. J. Cell. Sci., 115 (Pt 9): 1883-93. [PMID:11956320]

66. Paruchuri S, Sjölander A. (2003) Leukotriene D4 mediates survival and proliferation via separate but parallel pathways in the human intestinal epithelial cell line Int 407. J. Biol. Chem., 278 (46): 45577-85. [PMID:12912998]

67. Perng DW, Wu YC, Chang KT, Wu MT, Chiou YC, Su KC, Perng RP, Lee YC. (2006) Leukotriene C4 induces TGF-beta1 production in airway epithelium via p38 kinase pathway. Am. J. Respir. Cell Mol. Biol., 34 (1): 101-7. [PMID:16179583]

68. Pollock K, Creba J. (1990) Leukotriene D4 induced calcium changes in U937 cells may utilize mechanisms additional to inositol phosphate production that are pertussis toxin insensitive but are blocked by phorbol myristate acetate. Cell. Signal., 2 (6): 563-8. [PMID:1964390]

69. Porreca E, Di Febbo C, Di Sciullo A, Angelucci D, Nasuti M, Vitullo P, Reale M, Conti P, Cuccurullo F, Poggi A. (1996) Cysteinyl leukotriene D4 induced vascular smooth muscle cell proliferation: a possible role in myointimal hyperplasia. Thromb. Haemost., 76 (1): 99-104. [PMID:8819260]

70. Profita M, Sala A, Bonanno A, Siena L, Ferraro M, Di Giorgi R, Montalbano AM, Albano GD, Gagliardo R, Gjomarkaj M. (2008) Cysteinyl leukotriene-1 receptor activation in a human bronchial epithelial cell line leads to signal transducer and activator of transcription 1-mediated eosinophil adhesion. J. Pharmacol. Exp. Ther., 325 (3): 1024-30. [PMID:18305014]

71. Provost V, Langlois A, Chouinard F, Rola-Pleszczynski M, Chakir J, Flamand N, Laviolette M. (2012) Leukotriene D4 and interleukin-13 cooperate to increase the release of eotaxin-3 by airway epithelial cells. PLoS ONE, 7 (8): e43544. [PMID:22952702]

72. Pérez-Novo CA, Claeys C, Van Cauwenberge P, Bachert C. (2006) Expression of eicosanoid receptors subtypes and eosinophilic inflammation: implication on chronic rhinosinusitis. Respir. Res., 7: 75. [PMID:16689996]

73. Ravasi S, Capra V, Panigalli T, Rovati GE, Nicosia S. (2002) Pharmacological differences among CysLT(1) receptor antagonists with respect to LTC(4) and LTD(4) in human lung parenchyma. Biochem. Pharmacol., 63 (8): 1537-46. [PMID:11996896]

74. Ravasi S, Citro S, Viviani B, Capra V, Rovati GE. (2006) CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation. Respir. Res., 7: 42. [PMID:16553950]

75. 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]

76. Saegusa S, Tsubone H, Kuwahara M. (2001) Leukotriene D(4)-induced Rho-mediated actin reorganization in human bronchial smooth muscle cells. Eur. J. Pharmacol., 413 (2-3): 163-71. [PMID:11226389]

77. Saito K, Nagata M, Kikuchi I, Sakamoto Y. (2004) Leukotriene D4 and eosinophil transendothelial migration, superoxide generation, and degranulation via beta2 integrin. Ann. Allergy Asthma Immunol., 93 (6): 594-600. [PMID:15609771]

78. Sarau HM, Ames RS, Chambers J, Ellis C, Elshourbagy N, Foley JJ, Schmidt DB, Muccitelli RM, Jenkins O, Murdock PR et al.. (1999) Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor. Mol. Pharmacol., 56 (3): 657-63. [PMID:10462554]

79. Saussy Jr DL, Sarau HM, Foley JJ, Mong S, Crooke ST. (1989) Mechanisms of leukotriene E4 partial agonist activity at leukotriene D4 receptors in differentiated U-937 cells. J. Biol. Chem., 264 (33): 19845-55. [PMID:2555334]

80. Schierle S, Flauaus C, Heitel P, Willems S, Schmidt J, Kaiser A, Weizel L, Goebel T, Kahnt AS, Geisslinger G et al.. (2018) Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology. J. Med. Chem., 61 (13): 5758-5764. [PMID:29878767]

81. Sjölander A, Grönroos E, Hammarström S, Andersson T. (1990) Leukotriene D4 and E4 induce transmembrane signaling in human epithelial cells. Single cell analysis reveals diverse pathways at the G-protein level for the influx and the intracellular mobilization of Ca2+. J. Biol. Chem., 265 (34): 20976-81. [PMID:2174431]

82. Skoglund G, Claesson HE. (1991) Intracellular mechanisms involved in leukotriene C4-stimulated adhesion of U-937 cells. Cell. Signal., 3 (5): 399-404. [PMID:1760251]

83. Smith LJ, Greenberger PA, Patterson R, Krell RD, Bernstein PR. (1985) The effect of inhaled leukotriene D4 in humans. Am. Rev. Respir. Dis., 131 (3): 368-72. [PMID:3883862]

84. Suzuki S, Takeuchi K, Ishinaga H, Basbaum C, Majima Y. (2008) Leukotriene D4 upregulates MUC2 gene transcription in human epithelial cells. Pharmacology, 81 (3): 221-8. [PMID:18176092]

85. 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]

86. Thompson C, Cloutier A, Bossé Y, Thivierge M, Gouill CL, Larivée P, McDonald PP, Stankova J, Rola-Pleszczynski M. (2006) CysLT1 receptor engagement induces activator protein-1- and NF-kappaB-dependent IL-8 expression. Am. J. Respir. Cell Mol. Biol., 35 (6): 697-704. [PMID:16809637]

87. Thompson MD, Capra V, Takasaki J, Maresca G, Rovati GE, Slutsky AS, Lilly C, Zamel N, McIntyre Burnham W, Cole DE et al.. (2007) A functional G300S variant of the cysteinyl leukotriene 1 receptor is associated with atopy in a Tristan da Cunha isolate. Pharmacogenet. Genomics, 17 (7): 539-49. [PMID:17558309]

88. Ueda T, Takeno S, Furukido K, Hirakawa K, Yajin K. (2003) Leukotriene receptor antagonist pranlukast suppresses eosinophil infiltration and cytokine production in human nasal mucosa of perennial allergic rhinitis. Ann. Otol. Rhinol. Laryngol., 112 (11): 955-61. [PMID:14653364]

89. Vannella KM, McMillan TR, Charbeneau RP, Wilke CA, Thomas PE, Toews GB, Peters-Golden M, Moore BB. (2007) Cysteinyl leukotrienes are autocrine and paracrine regulators of fibrocyte function. J. Immunol., 179 (11): 7883-90. [PMID:18025235]

90. Virchow Jr JC, Faehndrich S, Nassenstein C, Bock S, Matthys H, Luttmann W. (2001) Effect of a specific cysteinyl leukotriene-receptor 1-antagonist (montelukast) on the transmigration of eosinophils across human umbilical vein endothelial cells. Clin. Exp. Allergy, 31 (6): 836-44. [PMID:11422147]

91. Weiss JW, Drazen JM, Coles N, McFadden Jr ER, Weller PF, Corey EJ, Lewis RA, Austen KF. (1982) Bronchoconstrictor effects of leukotriene C in humans. Science, 216 (4542): 196-8. [PMID:7063880]

92. Winkler JD, Sarau HM, Foley JJ, Crooke ST. (1988) Leukotriene D4-induced homologous desensitization in basal and differentiated U-937 cells: characterization with the partial agonist leukotriene E4 and assessment of receptor reserve. J. Pharmacol. Exp. Ther., 247 (1): 54-62. [PMID:2845060]

93. Woszczek G, Chen LY, Nagineni S, Kern S, Barb J, Munson PJ, Logun C, Danner RL, Shelhamer JH. (2008) Leukotriene D(4) induces gene expression in human monocytes through cysteinyl leukotriene type I receptor. J. Allergy Clin. Immunol., 121 (1): 215-221.e1. [PMID:18028998]

94. 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]

95. 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]

96. Yang G, Haczku A, Chen H, Martin V, Galczenski H, Tomer Y, Van Besien CR, Evans JF, Panettieri RA, Funk CD et al.. (2004) Transgenic smooth muscle expression of the human CysLT1 receptor induces enhanced responsiveness of murine airways to leukotriene D4. Am. J. Physiol. Lung Cell Mol. Physiol., 286 (5): L992-1001. [PMID:15064240]

97. Zhu J, Qiu YS, Figueroa DJ, Bandi V, Galczenski H, Hamada K, Guntupalli KK, Evans JF, Jeffery PK. (2005) Localization and upregulation of cysteinyl leukotriene-1 receptor in asthmatic bronchial mucosa. Am. J. Respir. Cell Mol. Biol., 33 (6): 531-40. [PMID:16123393]


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