Adenosine and dipyridamole: actions and interactions on the contractile response of guinea‐pig ileum to high frequency electrical field stimulation

Abstract

1 The action of adenosine on the myenteric plexus-longitudinal muscle strips from guinea-pig ileum to high frequency electrical field stimulation (10 Hz) was investigated. 2 Electrically induced contractions were reduced markedly by tetrodotoxin (0.2 μm) and atropine (1 μm), and partially by noradrenaline (3 μm) and morphine (3 μm). 3 Adenosine, adenosine 5′-monophosphate (AMP) and adenosine triphosphate (ATP) produced a concentration-dependent inhibition of the high frequency contractions over the range of 0.1–100 μm, the most potent being adenosine. 4 The concentration-response curve for adenosine was significantly shifted to the left by dipyridamole (10 nm), while dipyridamole at higher concentrations (30 nm–10 μm), depressed the contraction markedly by itself. 5 Dipyridamole decreased [³H]-adenosine uptake into strips of ileum in a concentration-dependent manner. There was a significant correlationship between the reduction of adenosine uptake and the inhibition of the contraction induced by dipyridamole (r = 0.970). 6 In strips desensitized to adenosine or treated with adenosine deaminase, the inhibitory effect of dipyridamole was significantly reduced. 7 The present investigation revealed that adenosine depressed responses of guinea-pig ileum to high frequency electrical stimulation and suggested that the inhibitory effect of dipyridamole may be closely associated with the behaviour of endogenous adenosine or related compounds.