Effects of CGS 21680, a selective adenosine A2A receptor agonist, on allergic airways inflammation in the rat

Fozard, John R.; Ellis, K M; Dantas, Maria Fernanda; Tigani, Bruno; Mazzoni, Lazzaro

doi:10.1016/s0014-2999(02)01305-5

Cited by 114 publications

(98 citation statements)

References 23 publications

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“…In a murine model of OVA-induced chronic obstructive pulmonary disease, A2a activation reduced influx of leukocytes into the BAL. Similar to our findings, pretreatment with CGS-21680 also reduced LPS-induced PMN infiltration (58,59) and cytokine release into the alveolar airspace, although not statistically significant in one study (59).…”

Section: Discussionsupporting

confidence: 90%

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Reutershan

Cagnina

Chang

et al. 2007

The Journal of Immunology

117

120

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To determine the role of the adenosine receptor A2a in a murine model of LPS-induced lung injury, migration of polymorphonuclear leukocytes (PMNs) into the different compartments of the lung was determined by flow cytometry, microvascular permeability was assessed by the extravasation of Evans blue, and the release of chemotactic cytokines into the alveolar airspace was determined by ELISA. Measurements were performed in wild-type and A2a gene-deficient mice (A2a−/−). To differentiate the role of A2a on hemopoietic and nonhemopoietic cells, we created chimeric mice by transfer of bone marrow (BM) between wild-type and A2a−/− mice and used mice that lacked A2a expression selectively on myeloid cells (A2aflox/flox × LysM-cre). A specific A2a receptor agonist (ATL202) was used to evaluate its potential to reduce lung injury in vivo. In wild-type mice, therapeutic treatment with ATL202 reduced LPS-induced PMN recruitment, and release of cytokines. Pretreatment, but not posttreatment, also reduced Evans blue extravasation. In the BM chimeric mice lacking A2a on BM-derived cells, PMN migration into the alveolar space was increased by ∼50%. These findings were confirmed in A2aflox/flox × LysM-cre mice. ATL202 was only effective when A2a was present on BM-derived cells. A2a agonists may be effective at curbing inflammatory lung tissue damage.

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Section: Discussionsupporting

confidence: 90%

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Reutershan

Cagnina

Chang

et al. 2007

The Journal of Immunology

117

120

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“…Immunosuppressive and anti-inflammatory properties observed after activation of A 2A receptors in the airways are well documented. Indeed, it was recently shown that the treatment with CGS21680, a selective agonist of the adenosine A 2A receptor, attenuates acute carrageenan-induced pleural and lung inflammation [33] and allergic pulmonary inflammation in rats [13]. Some studies also demonstrated that A 2A receptor activation may cause suppression of the recruitment of T lymphocytes to the lungs [34,35].…”

Section: Discussionmentioning

confidence: 99%

“…The potential role of adenosine triphosphate and adenosine in the pathogenesis of asthma has been supported by the bronchoconstrictor effects observed after their topical administration in the airways of patients with asthma and chronic obstructive pulmonary disease but not in those of healthy subjects [9][10][11][12]. In contrast, experimental data demonstrated that adenosine and its analogues have also been shown to exert protective and anti-inflammatory effects in the airways, reducing the leukocyte cell count in bronchoalveolar lavage fluid (BALF) and decreases airway remodelling in murine models of asthma, an effect related to adenosine A 2 receptors activation [13,14].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of inosine in allergic lung inflammation in mice: evidence for the participation of adenosine A2A and A3 receptors

Lapa

Oliveira

Accetturi

et al. 2013

Purinergic Signalling

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Inosine, a naturally occurring purine formed from the breakdown of adenosine, is associated with immunoregulatory effects. Evidence shows that inosine modulates lung inflammation and regulates cytokine generation. However, its role in controlling allergen-induced lung inflammation has yet to be identified. In this study, we aimed to investigate the role of inosine and adenosine receptors in a murine model of lung allergy induced by ovalbumin (OVA). Intraperitoneal administration of inosine (0.001-10 mg/kg, 30 min before OVA challenge) significantly reduced the number of leukocytes, macrophages, lymphocytes and eosinophils recovered in the bronchoalveolar lavage fluid of sensitized mice compared with controls. Interestingly, our results showed that pre-treatment with the selective A 2A receptor antagonist (ZM241385), but not with the selective A 2B receptor antagonist (alloxazine), reduced the inhibitory effects of inosine against macrophage count, suggesting that A 2A receptors mediate monocyte recruitment into the lungs. In addition, the pre-treatment of mice with selective A 3 antagonist (MRS3777) also prevented inosine effects against macrophages, lymphocytes and eosinophils. Histological analysis confirmed the effects of inosine and A 2A adenosine receptors on cell recruitment and demonstrated that the treatment with ZM241385 and alloxazine reverted inosine effects against mast cell migration into the lungs. Florianópolis 88040-900, Santa Catarina, Brazil Purinergic Signalling (2013) 9:325-336 DOI 10.1007 Accordingly, the treatment with inosine reduced lung elastance, an effect related to A 2 receptors. Moreover, inosine reduced the levels of Th 2 -cytokines, interleukin-4 and interleukin-5, an effect that was not reversed by A 2A or A 2B selective antagonists. Our data show that inosine acting on A 2A or A 3 adenosine receptors can regulate OVA-induced allergic lung inflammation and also implicate inosine as an endogenous modulator of inflammatory processes observed in the lungs of asthmatic patients.

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“…The antiinflammatory and tissue-protective properties of A 2A R agonists have not yet been adequately tested in clinical trials because the A 2A R has a widespread tissue and cell-type distribution, and therefore, activating this receptor might lead to unwanted side effects. The A 2A R activation mediates inhibition of platelet aggregation, hypotension and a variety of effects within the central nervous system [10,39,41]. In this respect, considering the low concentration of the A 2A R agonist and the inability of the A 2B R antagonist to penetrate the cell membrane as well as the blood-brain barrier, the concept of the agonist/antagonist combination could overcome these therapy limiting side effects.…”

Section: Discussionmentioning

confidence: 99%

Adenosine A2A agonist and A2B antagonist mediate an inhibition of inflammation-induced contractile disturbance of a rat gastrointestinal preparation

Michael

Warstat

Michel

et al. 2009

Purinergic Signalling

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Adenosine can show anti-inflammatory as well as pro-inflammatory activities. The contribution of the specific adenosine receptor subtypes in various cells, tissues and organs is complex. In this study, we examined the effect of the adenosine A 2A receptor agonist CGS 21680 and the A 2B R antagonist PSB-1115 on acute inflammation induced experimentally by 2,4,6-trinitrobenzenesulfonic acid (TNBS) on rat ileum/jejunum preparations. Preincubation of the ileum/jejunum segments with TNBS for 30 min resulted in a concentration-dependent inhibition of acetylcholine (ACh)-induced contractions. Pharmacological activation of the A 2A R with CGS 21680 (0.1-10 µM) preincubated simultaneously with TNBS (10 mM) prevented concentration-dependently the TNBS-induced inhibition of the ACh contractions. Stimulation of A 2B R with the selective agonist BAY 60-6583 (10 µM) did neither result in an increase nor in a further decrease of ACh-induced contractions compared to the TNBS-induced inhibition. The simultaneous pre-incubation of the ileum/jejunum segments with TNBS (10 mM) and the selective A 2B R antagonist PSB-1115 (100 µM) inhibited the contractiondecreasing effect of TNBS. The effects of the A 2A R agonist and the A 2B R antagonist were in the same range as the effect induced by 1 µM methotrexate. The combination of the A 2A R agonist CGS 21680 and the A 2B R antagonist PSB-1115 at subthreshold concentrations of both agents found a significant amelioration of the TNBS-diminished contractility. Our results demonstrate that the activation of A 2A receptors or the blockade of the A 2B receptors can prevent the inflammation-induced disturbance of the AChinduced contraction in TNBS pre-treated small intestinal preparations. The combination of both may be useful for the treatment of inflammatory bowel diseases.

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Effects of CGS 21680, a selective adenosine A2A receptor agonist, on allergic airways inflammation in the rat

Cited by 114 publications

References 23 publications

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Anti-inflammatory effects of inosine in allergic lung inflammation in mice: evidence for the participation of adenosine A2A and A3 receptors

Adenosine A2A agonist and A2B antagonist mediate an inhibition of inflammation-induced contractile disturbance of a rat gastrointestinal preparation

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