Spasmolytic effect of novel antagonists of the adenosine A2 receptor in isolated guinea pig tracheal smooth muscle

We have investigated the relaxation effect of nine novel adenosine A2B antagonists on precontracted guinea pig tracheas by carbachol (10 μM). Isometric contractions of isolated guinea pig tracheas were recorded at 2 g resting tension; and carbachol dose-response curves were performed. EC50 and IC50 values were identified by plotting cumulative concentration-response curve and pD2 values were calculated. Theophylline was able to relax carbachol precontracted tracheas on 10−3 M conc. The relaxant effect of 1 × 10−4 M compound 5 (ARR-1) was found highly significant as compared to theophylline (P < 0.001), whereas compound 6 (ARR-2) showed equipotent effect in a concentration dependent manner. However, other compounds were not able to attenuate contractions induced by carbachol significantly as compared to theophylline. Compound 5 (ARR-1) may be an important new compound in testing the current hypotheses proposing a therapeutic role for an adenosine antagonist in asthma. This effect might be attributed to inhibition of cAMP through adenyl cyclase enzyme. The results exclude an important contribution of adenosine A2B receptors.