Adenosine receptors: novel targets for drug development in allergic rhinitis

Matera, MG; Polosa, Riccardo

doi:10.1111/j.1365-2222.2006.02647.x

Cited by 7 publications

(4 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adenosine has long been implicated in a variety of inflammatory processes, including allergy and asthma (10)(11)(12)(13). This metabolite is produced and released under conditions of increased energy consumption, such as stress or hypoxia, where it then functions in an autocrine as well as paracrine fashion (10,14).…”

Section: All1 Inhibits A3r-activated Erk Signaling In Purified Rpmcs mentioning

confidence: 99%

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Baram

Dekel

Mekori

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Mast cells are key players in mediating and amplifying allergic and inflammatory reactions. Previously, we identified the G-protein, Gi3, as the cellular target of receptor mimetic basic secretagogues that activate mast cell independently of IgE. In this study, we demonstrate that Gi3 is the cellular target of the adenosine A3 receptor (A3R), a G-protein coupled receptor involved in inflammation and the pathophysiology of asthma. By using a cell permeable peptide comprising the C-terminal end of Gαi3 fused to an importation sequence (ALL1) as a selective inhibitor of Gi3 signaling, we show that by coupling to Gi3, the A3R stimulates multiple signaling pathways in human mast cells, leading to upregulation of cytokines, chemokines, and growth factors. We further show that after contact with activated T cell membranes, endogenous adenosine binds to and activates the A3R, resulting in Gi3-mediated signaling. Specifically, the majority of ERK1/2 signaling initiated by contact with activated T cell membranes, is mediated by Gi3, giving rise to ALL1-inhibitable cellular responses. These results unveil the physiological G-protein coupled receptor that couples to Gi3 and establish the important role played by this G-protein in inflammatory conditions that involve adenosine-activated mast cells.

show abstract

Section: All1 Inhibits A3r-activated Erk Signaling In Purified Rpmcs mentioning

confidence: 99%

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Baram

Dekel

Mekori

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Secondly, adenosine receptor subtypes involved in adenosine‐induced bronchoconstriction and inflammatory responses vary among species and this makes the clinical relevance of data obtained in animal models unclear. In addition, the specific tissue and cell type distribution of adenosine receptors in human upper and lower airways is not clear (32, 33). Thirdly, it could be argued that the dose of the A 2A agonist we used (25 μg, twice daily) was subtherapeutic either because of a too low dose or too short duration of therapy.…”

Section: Discussionmentioning

confidence: 81%

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

Luijk¹,

Berge²,

Kerstjens³

et al. 2007

Allergy

View full text Add to dashboard Cite

show abstract

“…Adenosine has been long implicated in a variety of inflammatory processes, including allergy and especially asthma (Bours et al, 2006; Spicuzza et al, 2006; Matera and Polosa, 2007; Brown et al, 2008; Polosa and Blackburn, 2009). That MCs mediate adenosine responses in allergic inflammation was first indicated by the ability of adenosine to potentiate IgE-induced mediator release from rodent MCs (Holgate et al, 1980).…”

Section: Adenosine and Mc-mediated Inflammationmentioning

confidence: 99%

Mast Cell Adenosine Receptors Function: A Focus on the A3 Adenosine Receptor and Inflammation

Rudich¹,

Ravid²,

Sagi‐Eisenberg³

2012

Front. Immun.

View full text Add to dashboard Cite

Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease patients, but not in non-asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells (MCs), as an attractive drug candidate. Four subtypes (A1, A2a, A2b, and A3) of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R) in mediating hyper responsiveness to adenosine in MCs, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human MCs. The relevance of mouse studies to the human is discussed.

show abstract

Adenosine receptors: novel targets for drug development in allergic rhinitis

Cited by 7 publications

References 26 publications

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

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

Mast Cell Adenosine Receptors Function: A Focus on the A3 Adenosine Receptor and Inflammation

Contact Info

Product

Resources

About

Adenosine receptors: novel targets for drug development in allergic rhinitis

Cited by 7 publications

References 26 publications

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

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

Mast Cell Adenosine Receptors Function: A Focus on the A3 Adenosine Receptor and Inflammation

Contact Info

Product

Resources

About

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