The identification of the adenosine receptor subtypes and a better understanding of their activity with different cell populations have helped us to understand the action of adenosine in the lung.2–3
There appear to be four separate adenosine receptors in lung tissue.2–3
The classic adenosine receptor, A1, is found primarily in smooth muscle and nerve tissue, and it causes a reduction in cyclic adenosine monophosphate (cAMP), leading to direct or neurogenic mediated bronchospasm. The A2a receptor, which is found in the mast cell and in the bronchial epithelium, causes an increase in cAMP, thereby inhibiting the release of the mediators of inflammation from mast cells. The A2b receptor, which is closely related to the A2a receptor, is also found in the bronchial epithelium and mast cells. This receptor utilizes different signal-transducing systems than does the A2a receptor. As a result, the A2b receptor stimulates the release of mediators from the mast cell, thereby increasing bronchial reactivity. Among the mast cell mediators that have been shown to be released by the A2b adenosine receptor are tryptase, histamine, interleukins, lypoxygenase products, and other cytokines. The A2a receptor activity predominates at low adenosine concentrations, while the A2b effect predominates at high adenosine concentrations. Finally, the A3 receptor, which is less well-characterized but is known to be present in lung tissue, acts very much like the A1 receptor, reducing cAMP levels. The net result is that the stimulation of the A1 receptor, the A2b receptor, or the A3 receptor leads to bronchoconstriction by both direct and indirect methods. The stimulation of the A2a receptor, on the other hand, would lead to a bronchodilation by inhibiting the mast cell release of mediators of the immune response.