Adenosine inhibition of isolated rabbit ileum and antagonism by theophylline

The spontaneously contracting isolated rabbit ileum was used to study adenosine stimulated receptors. The inhibitory effects of adenosine were not reduced by pretreating the rabbits with either reserpine of 6-hydroxydopamine which were used to eliminate adrenergic function. Similarly the addition of tetrodotoxin to the muscle bath had no effect on the ability of adenosine to produce its inhibitory response. Of the compounds tested for agonistic activity, adenosine and ATP were the most potent (ED50 6 X 10(-7) M). The inhibition by adenosine was antagonized by both theophylline and caffeine in a surmountable manner. Theophylline analogs with charged substituents in position 7 were without antagonist activity. The results suggest that 1) receptors for adenosine or adenine nucleotides are located on the smooth muscle cells of rabbit ileum, 2) receptor stimulation requires and intact adenosine moiety and 3) methylxanthines exert their antagonistic effects by acting as competitive antagonists.