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

Abstract

1 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. 2 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. 3 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. 4 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. 5 It is concluded that the potentiation of adenosine by diazepam is possibly due to an inhibition of adenosine uptake.