Inhibition of noradrenaline release by adenosine.

1. Release of [3H]noradrenaline evoked by stimulation (5 Hz) of the pre-labelled rat vas deferens was reduced to 50% by adenosine (10(-6) g/ml.). Inhibition of release was dependent on the concentration of adenosine and was inversely related to the frequency of stimulation. Phenoxybenzamine did not interfere with the action of adenosine on release. 2. Exposure of the pre-labelled rat vas deferens to 135 mM-K+ released almost 10 times more [3H]noradrenaline than exposure to 45 mM-K+. Release induced by 45 mM-K+ was almost abolished by adenosine (10(-6) g/ml.) but that induced by 135 mM-K+ was reduced to only 45%. 3. Inhibition of [3H]noradrenaline release was observed in salivary gland, heart and portal vein of the rat, and in the guinea-pig heart and vas deferens. A very high concentration of adenosine (10(-4) g/ml.) reduced the release (about 50%) in the rabbit heart, but the cat heart was totally insensitive to the inhibitory action of adenosine. 4. Aminophylline (2 x 10(-4) g/ml.) antagonized the inhibitory action of adenosine (10(-6) g/ml.) on the release of [3H]noradrenaline in the phenoxybenzamine-treated vas deferens. 5. Tetraethylammonium (8 x 10(-4) g/ml.) enhanced stimulation-evoked release in the rat salivary gland by almost tenfold. In the presence of tetraethylammonium, even higher concentrations (2 x 10(-5) g/ml.) of adenosine failed to interfere with release. 6. Elevation of external K+ (19 mM) blocked stimulation-evoked release in the rat vas deferens by about 55%. Combination of high K+ and adenosine (10(-6) g/ml.), which blocked release by about 40%, caused still greater inhibition (80%) of the release. 7. The possible mechanism of action of the inhibitory effect of adenosine on the stimulation-evoked release of noradrenaline is discussed in relation to the calcium hypothesis.