Inhibition of fundic strips from guinea-pig stomach: The effect of theophylline on responses to adenosine, ATP and intramural nerve stimulation

The effect of theophylline on the ATP response, the adenosine response and the inhibitory junction potential was studied on circular smooth muscle preparations of the guinea-pig stomach. The amplitude of the inhibitory junction potential evoked after stimulation of the non-cholinergic, non-adrenergic nervous system was not affected by a moderate concentration of theophylline (5 x 10(-6)-10(-5) M). At higher concentrations (5 x 10(-5)-10(-3) M) theophylline relaxed the muscle hyperpolarized the cell membrane and reduced the inhibitory junction potential slightly. ATP and adenosine (5 x 10(-6)-10(-3) M) also caused relaxation of the smooth muscle cells and hyperpolarization of the cell membrane. Theophylline (5 x 10(-6)-10(-3) M) did not antagonize these effects; in the presence of theophylline (5 x 10(-5)-10(-3) M) additional relaxations produced by ATP and adenosine were limited in view of the muscle tone. These results indicate that theophylline does not inhibit either the effect of the non-adrenergic inhibitory transmitter on the smooth muscle cells of the guinea-pig stomach or the actions of ATP and adenosine. This suggests that the existence of theophylline-sensitive adenosine receptors in the stomach-muscle cell membrane is unlikely and that theophylline is not the drug of choice to support the purinergic nerve hypothesis.