Potentiation of pharmacological responses to adenosine, in vitro and in vivo

1. In washed guinea-pig brain slices, adenosine uptake inhibitors potentiated the responsiveness of cAMP to adenosine, while an adenosine deaminase inhibitor, 2'-deoxycoformycin, was without effect. 2. In the isolated guinea-pig ileum, uptake was important in terminating the inhibitory action of adenosine on nerve-mediated contractions whereas the ADA inhibitor did not affect the ileum or its responses to adenosine in any way. 3. Adenosine given to mice (100 mg/kg i.p.) or guinea-pigs (250 mg/kg i.p.) caused a small, transient fall in body temperature, accompanied by skeletal-muscle relaxation. 4. In mice this temperature fall was potentiated by the uptake blocker dilazep, although only marginally so by the uptake blocker dipyridamole. The ADA-inhibitor also potentiated the pharmacological responses to adenosine. 5. Responses to adenosine in the guinea-pig were less affected by treatment with uptake or ADA-inhibitors, except when given in combination.