A₁ antagonism in asthma: better than coffee?
J. Clin. Invest. Stephen L. Tilley, et al. 115:13 doi:10.1172/JCI24009 [Go to this article.]

Figure 2
Model of receptors and cell types mediating the pro- and anti-inflammatory effects of adenosine in the lung. Proinflammatory pathways are depicted in red while anti-inflammatory pathways are depicted in blue. A₃ receptor activation has been implicated in a number of proinflammatory events including mast cell–dependent increases in vasopermeability, adenosine-induced mast cell degranulation, enhancement of antigen-induced mast cell degranulation, mucus metaplasia and secretion, and recruitment of eosinophils and neutrophils to the airway. It remains unclear whether this chemotactic effect of adenosine on granulocytes is due to direct activation of A₃ receptors on these leukocytes or indirect activation through A₃-induced mediator release by other cell types, such as mast cells. A_2B receptors have also been implicated in mediating mast cell activation by adenosine. IL-13 and adenosine have been shown to stimulate one another in an amplification pathway that may contribute to the proinflammatory capacity of each mediator. Macrophages play an important anti-inflammatory role in asthma, and adenosine sends anti-inflammatory signals to macrophages through A₁ and A₃ receptors. These effects may occur through both the enhanced release of anti-inflammatory mediators, such as IL-10 and PGE₂, and the inhibition of release of proinflammatory mediators, including TNF-α and MMPs. Adenosine elicits bronchoconstriction in the asthmatic airway both directly from the activation of A1 receptors on airway smooth muscle and indirectly by bronchoconstrictive substances released by mast cells. A2A receptors are believed to send anti-inflammatory signals to all cell types on which they are expressed. Events depicted in the interstitium may also occur in the airway lumen.