Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this article is to review the interplay between adenosine and mast cells in asthma. Adenosine is an endogenous nucleoside released from metabolically active cells and generated extracellularly via the degradation of released ATP. It is a potent biological mediator that modulates the activity of numerous cell types including platelets, neutrophils and mast cells via action at specific adenosine receptors (A1, A2a, A2b, A3). These receptors are expressed on mast cells but the exact pattern of receptor subtype expression depends on the source of the mast cells. Adenosine is also a potent bronchoconstricting agent and is suggested to contribute to the pathophysiology of asthma. Evidence is provided to suggest that the nucleoside exerts its influence on the asthmatic condition through its ability to modulate the release of mast cell derived mediators. However, the mechanism of adenosine/mast cell interaction which contributes to asthma remains unclear. Progress in the area has been hampered by the heterogeneity of mast cell responses and a lack of highly specific receptor agonists and antagonists. The expression of different adenosine receptor subtypes on mast cells is described. The final section of the review presents data to suggest that BAL mast cells may provide an accurate and relevant model for future investigations and together with the development of superior pharmacological tools, may aid the realisation of the therapeutic potential of adenosine/mast cell interactions in asthma. In conclusion, the role of adenosine in asthma is clearly complex. A better understanding of the contribution of adenosine to the asthmatic condition may lead to novel therapeutic approaches in the treatment of the disease.
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PMID:Adenosine, mast cells and asthma. 1044 81

Pseudomonas aeruginosa infections are increasingly multidrug resistant and cause healthcare-associated pneumonia, a major risk factor for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Adenosine is a signaling nucleoside with potential opposing effects; adenosine can either protect against acute lung injury via adenosine receptors or cause lung injury via adenosine receptors or equilibrative nucleoside transporter (ENT)-dependent intracellular adenosine uptake. We hypothesized that blockade of intracellular adenosine uptake by inhibition of ENT1/2 would increase adenosine receptor signaling and protect against P. aeruginosa-induced acute lung injury. We observed that P. aeruginosa (strain: PA103) infection induced acute lung injury in C57BL/6 mice in a dose- and time-dependent manner. Using ENT1/2 pharmacological inhibitor, nitrobenzylthioinosine (NBTI), and ENT1-null mice, we demonstrated that ENT blockade elevated lung adenosine levels and significantly attenuated P. aeruginosa-induced acute lung injury, as assessed by lung wet-to-dry weight ratio, BAL protein levels, BAL inflammatory cell counts, pro-inflammatory cytokines, and pulmonary function (total lung volume, static lung compliance, tissue damping, and tissue elastance). Using both agonists and antagonists directed against adenosine receptors A2AR and A2BR, we further demonstrated that ENT1/2 blockade protected against P. aeruginosa -induced acute lung injury via activation of A2AR and A2BR. Additionally, ENT1/2 chemical inhibition and ENT1 knockout prevented P. aeruginosa-induced lung NLRP3 inflammasome activation. Finally, inhibition of inflammasome prevented P. aeruginosa-induced acute lung injury. Our results suggest that targeting ENT1/2 and NLRP3 inflammasome may be novel strategies for prevention and treatment of P. aeruginosa-induced pneumonia and subsequent ARDS.
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PMID:Blockade of equilibrative nucleoside transporter 1/2 protects against Pseudomonas aeruginosa-induced acute lung injury and NLRP3 inflammasome activation. 3191 98