Effect of an inhaled adenosine A<sub>2A</sub> agonist on the allergen‐induced late asthmatic response

Luijk, Bart; Berge, van den Maarten; Kerstjens, Huib A. M.; Postma, Dirkje S.; Cass, Lindsey; Sabin, A. T.; Lammers, J.-W. J.

doi:10.1111/j.1398-9995.2007.01557.x

Cited by 44 publications

(31 citation statements)

References 34 publications

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“…In this study, treatment with GW328267X delivered as an inhalational treatment did not protect against the late asthmatic response (LAR), expressed as the decline in FEV 1 after allergen challenge, or the accompanying increase in airway inflammation (Luijk et al 2008). However, in an earlier study, GW328267X partially inhibited the early asthmatic response (EAR) and LAR after nasal allergen challenge in patients with allergic rhinitis (Rimmer et al 2007).…”

Section: Adenosine Receptors In Asthmamentioning

confidence: 60%

“…Recently, the effects of a new A 2A AR agonist, GW328267X, in human asthmatics was reported (Luijk et al 2008). In this study, treatment with GW328267X delivered as an inhalational treatment did not protect against the late asthmatic response (LAR), expressed as the decline in FEV 1 after allergen challenge, or the accompanying increase in airway inflammation (Luijk et al 2008).…”

Section: Adenosine Receptors In Asthmamentioning

confidence: 99%

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Adenosine Receptors and Asthma

Wilson

Nadeem

Spina

et al. 2009

Adenosine Receptors in Health and Disease

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The pathophysiological processes underlying respiratory diseases like asthma are complex, resulting in an overwhelming choice of potential targets for the novel treatment of this disease. Despite this complexity, asthmatic subjects are uniquely sensitive to a range of substances like adenosine, thought to act indirectly to evoke changes in respiratory mechanics and in the underlying pathology, and thereby to offer novel insights into the pathophysiology of this disease. Adenosine is of particular interest because this substance is produced endogenously by many cells during hypoxia, stress, allergic stimulation, and exercise. Extracellular adenosine can be measured in significant concentrations within the airways; can be shown to activate adenosine receptor (AR) subtypes on lung resident cells and migrating inflammatory cells, thereby altering their function, and could therefore play a significant role in this disease. Many preclinical in vitro and in vivo studies have documented the roles of the various AR subtypes in regulating cell function and how they might have a beneficial impact in disease models. Agonists and antagonists of some of these receptor subtypes have been developed and have progressed to clinical studies in order to evaluate their potential as novel antiasthma drugs. In this chapter, we will highlight the roles of adenosine and AR subtypes in many of the characteristic features of asthma: airway obstruction, inflammation, bronchial hyperresponsiveness and remodeling. We will also discuss the merit of targeting each receptor subtype in the development of novel antiasthma drugs.

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Section: Adenosine Receptors In Asthmamentioning

confidence: 60%

Section: Adenosine Receptors In Asthmamentioning

confidence: 99%

Adenosine Receptors and Asthma

Wilson

Nadeem

Spina

et al. 2009

Adenosine Receptors in Health and Disease

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show abstract

“…It is possible that the environment in which the mast cell resides influences adenosine receptor expression and function, accounting for the differences in receptor effects observed between these studies. Although several studies have suggested that A 2A receptors mediate anti-inflammatory effects (Antonioli et al, 2010;Fenster et al, 2000;Harada et al, 2000;Kreckler et al, 2006;Rork et al, 2008;Trevethick et al, 2008), a clinical trial failed to demonstrate efficacy of an A 2A agonist in attenuating allergen-induced early and late reactions, sputum total cell counts and EG21 cell numbers, eosinophil cationic protein levels, or inflammatory cytokine production in asthmatic subjects (Luijk et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

G_s-Coupled Adenosine Receptors Differentially Limit Antigen-Induced Mast Cell Activation

Hua

Chason

Jania

et al. 2012

J Pharmacol Exp Ther

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Mast cell activation results in the immediate release of proinflammatory mediators prestored in cytoplasmic granules, as well as initiation of lipid mediator production and cytokine synthesis by these resident tissue leukocytes. Allergen-induced mast cell activation is central to the pathogenesis of asthma and other allergic diseases. Presently, most pharmacological agents for the treatment of allergic disease target receptors for inflammatory mediators. Many of these mediators, such as histamine, are released by mast cells. Targeting pathways that limit antigen-induced mast cell activation may have greater therapeutic efficacy by inhibiting the synthesis and release of many proinflammatory mediators produced in the mast cell. In vitro studies using cultured human and mouse mast cells, and studies of mice lacking A 2B receptors, suggest that adenosine receptors, specifically the G s -coupled A 2A and A 2B receptors, might provide such a target. Here, using a panel of mice lacking various combinations of adenosine receptors, and mast cells derived from these animals, we show that adenosine receptor agonists provide an effective means of inhibition of mast cell degranulation and induction of cytokine production both in vitro and in vivo. We identify A 2B as the primary receptor limiting mast cell degranulation, whereas the combined activity of A 2A and A 2B is required for the inhibition of cytokine synthesis.

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“…Activation of A2A has been reported to suppress key components of the inflammatory process, including leukocyte recruitment, phagocytosis, pro-inflammatory cytokine production, and immune cell proliferation [26,27]. These findings have already led to the clinical testing of A2A agonists in the treatment of inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and diabetic foot ulcer [27][28][29]. The beneficial effect of A2A antagonist in EAE animals suggests that A2A receptors in the CNS might play an opposite role compared to the A2A receptors expressed on immune cells, though the functions of CNS A2A receptors are yet to be defined in autoimmune diseases.…”

Section: Adenosine Receptorsmentioning

confidence: 99%

G protein-coupled receptors as therapeutic targets for multiple sclerosis

Xie

2012

Cell Res

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G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants. They are considered as the most successful therapeutic targets for a broad spectrum of diseases. Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). It is the leading cause of non-traumatic disability in young adults. Great progress has been made over the past few decades in understanding the pathogenesis of MS. Numerous data from animal and clinical studies indicate that many GPCRs are critically involved in various aspects of MS pathogenesis, including antigen presentation, cytokine production, T-cell differentiation, T-cell proliferation, T-cell invasion, etc. In this review, we summarize the recent findings regarding the expression or functional changes of GPCRs in MS patients or animal models, and the influences of GPCRs on disease severity upon genetic or pharmacological manipulations. Hopefully some of these findings will lead to the development of novel therapies for MS in the near future.

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Effect of an inhaled adenosine A_2A agonist on the allergen‐induced late asthmatic response

Abstract: The inhaled A(2A)-receptor agonist, GW328267X, 25 microg does not affect the allergen-induced LAR or the associated inflammatory response in asthma.

Cited by 44 publications

References 34 publications

Adenosine Receptors and Asthma

Adenosine Receptors and Asthma

G_s-Coupled Adenosine Receptors Differentially Limit Antigen-Induced Mast Cell Activation

G protein-coupled receptors as therapeutic targets for multiple sclerosis

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Effect of an inhaled adenosine A2A agonist on the allergen‐induced late asthmatic response

Abstract: The inhaled A(2A)-receptor agonist, GW328267X, 25 microg does not affect the allergen-induced LAR or the associated inflammatory response in asthma.

Cited by 44 publications

References 34 publications

Adenosine Receptors and Asthma

Adenosine Receptors and Asthma

Gs-Coupled Adenosine Receptors Differentially Limit Antigen-Induced Mast Cell Activation

G protein-coupled receptors as therapeutic targets for multiple sclerosis

Contact Info

Product

Resources

About

Effect of an inhaled adenosine A_2A agonist on the allergen‐induced late asthmatic response

G_s-Coupled Adenosine Receptors Differentially Limit Antigen-Induced Mast Cell Activation