A ROLE FOR ADENOSINE IN ASTHMA? selectively (vis á vis histamine) blocks adenosine bronchoconstriction in asthmatics and has affinity for the A role for adenosine in asthma has been postulated adenosine A2B receptor at concentrations achieved clinically. Significantly, both rebound hyperreactivity for many years and there have been several recent reviews which have set out in detail the key evidence to adenosine and exacerbation of symptoms has been reported when treatment with theophylline is dissupporting the proposal. 1–4 Reference support for the statements made in the summary which follows can continued. Taken together, the evidence implicates adenosine be found in these reviews. All animal tissues possess the means to produce asanimportantmediatorincertainofthefundamental events underlying the inflammatory process of allergic and metabolize adenosine. Its formation is facilitated inter alii by hypoxia and by immuno-inflammatory cell asthma. activation, conditions which prevail in the asthmatic lung. Consistent with this, both venous plasma and bronchoalveolar (BAL) fluid concentrations of ad- ADENOSINE RECEPTOR SUBTYPES enosine are markedly increased following antigen challenge in asthmatics. The properties and location of the four recognized adenosine receptor subtypes are summarized in Adenosine constricts asthmatic, but not non-asthmatic, human bronchi both in vitro and in vivo. Table 1. Consideration of the responses mediated by the Bronchoconstriction in asthma patients is accompanied by an increase in venous plasma histamine receptor subtypes and their location in respiratory smooth muscle and/or immuno-inflammatory cells concentrationsandanaugmentationofthehistamine, PGD2 and tryptase concentrations in BAL fluid. important in asthma or COPD pathophysiology, suggests that agonists and/or antagonists at adenosine Blockade of adenosine-induced bronchoconstriction by antihistaminics, sodium cromoglycate and nedo- receptors may have the potential to provide novel approaches to the treatment of asthma. cromil, and non-steroidal antiinflammatory drugs provides strong evidence for mast cell involvement in the adenosine response in asthmatics. Perhaps of greater significance than an effect directly to degranulate mast ADENOSINE A1 RECEPTORS cells is the capacity of adenosine to potentiate the immunological and non-immunological activation of In an allergic rabbit model having many similarities with allergic asthma, rabbits immunized at birth with both animal and human mast cells. Enhancement of the response to allergen challenge by adenosine antigen have been found to develop airways hyperreactivity to adenosine. 7 The mechanism involves upreceptor agonists can be demonstrated in rodents and adenosine monophosphate (AMP) increases the regulation of the A1 receptor as a consequence of the immunization, 7–9 and qualitatively mimics the situimmediate response to allergen challenge in man. More direct evidence of a role for adenosine in ation in man where airway responses to adenosine are more prominent in allergic asthmatics than in asthma includes the fact that dipyridamole, a blocker of facilitated adenosine update, augments AMP-in- non-asthmatics In an elegant extension to these studies Nyce and duced bronchoconstriction and precipitates severe bronchospasm in asthmatic patients, and that cross- Metzger, 10 confirmed that the A1 receptor mediates bronchoconstriction to adenosine in the rabbit by tachyphylaxis can be demonstrated between AMP and exercise-induced asthma. Finally, theophylline using antisense oligo-deoxynucleotides targeted