Effects of methylxanthines and imidazole on the contractions of guinea-pig ileum induced by transmural stimulation.

Methylxanthines (10(-5) to 10(-3)M) were found to increase the amplitude of contractions of guinea-pig ileum induced by transmural stimulation but to inhibit those induced by acetylcholine or histamine. The order of the abilities of methylxanthines to augment the contractile responses was theobromine greater than caffeine greater than theophylline. When the contractions were completely suppressed by reduction of the calcium content in the medium or by addition of cyclic AMP, methylxanthines restored the responses effectively, just as does addition of calcium. Methylxanthines also accelerated the release of acetylcholine from the ileum associated with stimulation. Imidazole (3 X 10(-5) to 10(-3) M) had an essentially similar effect to methylxanthines in potentiating the contractile responses and in augmenting the release of acetylcholine. The present results indicate that the potentiating effects of methylxanthines and imidazole are due to an action on the nerve terminals, not on the postsynaptic membranes or contractile elements. Therefore, it si concluded that theit potentiating actions are due to facilitation of the movement of calcium in the nerve terminals on excitation, resulting in increased release of acetylcholine, and are not due to the effect of cyclic AMP formed as a result of their inhibitory actions on phosphodiesterase.