POTENTIATION OF THE EFFECTS OF ADENOSINE ON ISOLATED CARDIAC AND SMOOTH MUSCLE BY DIAZEPAM

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Abstract
Adenosine (10−7 to 3 times 10−4 m) or 2‐chloroadenosine (10−8 to 10−5 m) produced concentration‐dependent inhibition of the responses of the rat isolated vas deferens to electrical field stimulation. In electrically driven (2 Hz) guinea‐pig isolated left atria, adenosine (10−6 to 10−3 m) or 2‐chloroadenosine (10−8 to 10−7 m) produced concentration‐dependent decreases in isometric tension. Diazepam (10−6 and 10−5 m) had no direct effect per se, but significantly potentiated the inhibitory action of adenosine on both tissues without altering the inhibitory effect of 2‐chloroadenosine. The adenosine uptake inhibitors, hydroxynitrobenzylthioguanosine (HNBTG, 10−5 m) and dipyridamole (10−5 m) also potentiated the inhibitory actions of adenosine in rat vas deferens, but not those of 2‐chloroadenosine. Following adenosine uptake inhibition in rat vas deferens by HNBTG (10−5 m), diazepam (10−5 m) failed to produce any significant further potentiation of the inhibitory action of adenosine. It is concluded that the potentiation of adenosine by diazepam is possibly due to an inhibition of adenosine uptake.