Cysteinyl leukotriene receptor 1 is also a pyrimidinergic receptor and is expressed by human mast cells

Mellor, Elizabeth A.; Maekawa, Akiko; Austen, K. Frank; Boyce, Joshua A.

doi:10.1073/pnas.141221498

Cited by 160 publications

(173 citation statements)

References 31 publications

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“…A relationship between UDP and the CysLT 1 receptor has already been suggested, with the hypothesis that UDP may act directly on the receptor [42,43].…”

Section: Discussionmentioning

confidence: 97%

CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors

Mamedova

Capra

Accomazzo

et al. 2005

Biochemical Pharmacology

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Montelukast and pranlukast are orally active leukotriene receptor antagonists selective for the CysLT 1 receptor. Conversely, the hP2Y 1,2,4,6,11,12,13,14 receptors represent a large family of GPCRs responding to either adenine or uracil nucleotides, or to sugar-nucleotides. Montelukast and pranlukast were found to inhibit nucleotide-induced calcium mobilization in a human monocyte-macrophage like cell line, DMSO-differentiated U937 (dU937). Montelukast and pranlukast inhibited the effects of UTP with IC 50 values of 7.7 and 4.3 μM, respectively, and inhibited the effects of UDP with IC 50 values of 4.5 and 1.6 μM, respectively, in an insurmountable manner. Furthermore, ligand binding studies using [ 3 H]LTD 4 excluded the possibility of orthosteric nucleotide binding to the CysLT 1 receptor. dU937 cells were shown to express P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2Y 13 and P2Y 14 receptors. Therefore, these antagonists were studied functionally in a heterologous expression system for the human P2Y receptors. In 1321N1 astrocytoma cells stably expressing human P2Y 1,2,4,6 receptors, CysLT 1 antagonists inhibited both the P2Y agonist-induced activation of phospholipase C and intracellular Ca 2+ mobilization. IC 50 values at P2Y 1 and P2Y 6 receptors were <1 μM. In control astrocytoma cells expressing an endogenous M3 muscarinic receptor, 10 μM montelukast had no effect on the carbachol-induced rise in intracellular Ca 2+ . These data demonstrated that CysLT 1 receptor antagonists interact functionally with signaling pathways of P2Y receptors, and this should foster the study of possible implications for the clinical use of these compounds in asthma or in other inflammatory conditions.

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“…A relationship between UDP and the CysLT 1 receptor has already been suggested, with the hypothesis that UDP may act directly on the receptor [42,43].…”

Section: Discussionmentioning

confidence: 97%

CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors

Mamedova

Capra

Accomazzo

et al. 2005

Biochemical Pharmacology

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“…Utilizing Cys-LT receptors, these mediators exert a diverse range of inflammatory effects including bronchoconstriction, smooth muscle proliferation, airway remodelling, fibrosis, and effector cell recruitment and activation [155]. Two known Cys-LT receptors, CysLT1 and CysLT2, have been characterized on a number of inflammatory cells, including mast cells [156,157]. 5-LO inhibitors and CysLT1 receptor antagonists are Histamine released by activated mast cells induces vasodilation, vascular permeability, and smooth muscle contraction in tissues via histamine receptors.…”

Section: Extracellular Targetsmentioning

confidence: 99%

The mast cell and allergic diseases: role in pathogenesis and implications for therapy

Brown

Wilson

Metcalfe

2007

Clin Experimental Allergy

242

184

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SummaryMast cells have long been recognized for their role in the genesis of allergic inflammation; and more recently for their participation in innate and acquired immune responses. Mast cells reside within tissues including the skin and mucosal membranes, which interface with the external environment; as well as being found within vascularized tissues next to nerves, blood vessels and glandular structures. Mast cells have the capability of reacting both within minutes and over hours to specific stimuli, with local and systemic effects. Mast cells express the high affinity IgE receptor (FceRI) and upon aggregation of FceRI by allergen-specific IgE, mast cells release and generate biologically active preformed and newly synthesized mediators which are involved in many aspects of allergic inflammation. While mast cells have been well documented to be essential for acute allergic reactions, more recently the importance of mast cells in reacting through pattern recognition receptors in innate immune responses has become recognized. Moreover, as our molecular understanding of the mast cell has evolved, novel targets for modulation have been identified with promising therapeutic potential.

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“…To date, pharmacological studies identified two receptors for cys-LTs, named CysLT1 and CysLT2, whose characteristics were then largely confirmed by molecular biology studies that allowed the cloning of two genes for the human CysLT1 and CysLT2 receptors [5].…”

Section: Introductionmentioning

confidence: 95%

Innovative functional cAMP assay for studying G protein-coupled receptors: application to the pharmacological characterization of GPR17

Buccioni

Marucci

Ben

et al. 2011

Purinergic Signalling

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In this work, an innovative and non-radioactive functional cAMP assay was validated at the GPR17 receptor. This assay provides a simple and powerful new system to monitor G protein-coupled receptor activity through change in the intracellular cAMP concentration by using a mutant form of Photinus pyralis luciferase into which a cAMP-binding protein moiety has been inserted. Results, expressed as EC 50 or IC 50 values for agonists and antagonists, respectively, showed a strong correlation with those obtained with [ 35 S]GTPγS binding assay, thus confirming the validity of this approach in the study of new ligands for GPR17. Moreover, this method allowed confirming that GPR17 is coupled with a G αi .

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Cysteinyl leukotriene receptor 1 is also a pyrimidinergic receptor and is expressed by human mast cells

Cited by 160 publications

References 31 publications

CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors

CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors

The mast cell and allergic diseases: role in pathogenesis and implications for therapy

Innovative functional cAMP assay for studying G protein-coupled receptors: application to the pharmacological characterization of GPR17

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