THE EFFECTS OF DIPYRIDAMOLE ON THE GUINEA‐PIG ILEAL LONGITUDINAL MUSCLE‐MYENTERIC PLEXUS PREPARATION

Abstract

1 The longitudinal muscle-myenteric plexus strip prepared from guinea-pig ileum has been used to study the actions of dipyridamole and its interactions with adenine derivatives. 2 Dipyridamole augmented the inhibitory effects of adenine derivatives on the twitch response induced by 0.1 Hz field stimulation of the preparation. This synergistic effect was apparent with relatively low concentrations of dipyridamole (10 to 100 nM) and after short pretreatment times (1 to 2 min) that did not inhibit the twitch response on their own. Appropriate studies suggested the dipyridamole-adenosine synergism followed a pattern of facilitative agonist competition. 3 Dipyridamole did not inhibit either uptake of [3H]-adenosine by the preparation or adenosine deaminase activity under the same conditions that it exhibited synergism with adenosine. 4 Higher concentrations of dipyridamole inhibited the twitch response, mainly by decreasing acetylcholine release but partly by a direct action on smooth muscle. The direct action of dipyridamole on muscle was not synergistic with adenosine. 5 Fluorescence microscopy showed preferential binding of dipyridamole to the myenteric plexus.