Antagonistic effects of theophylline and adenosine on adrenergic neuroeffector transmission in the rabbit kidney

Abstract

The actions of adenosine and theophylline on adrenergic neuroeffector transmission were studied in the rabbit kidney perfused with Tyrode's solution in which the norepinephrine stores had been labeled with (-)-norepinephrine[3H] ((-)-NE[3H]). We found that adenosine inhibited (-)-NE[3H] release induced by nerve stimulation, increased basal perfusion pressure, and enhanced the vasoconstrictor response to nerve stimulation and norepinephrine in a dose-dependent manner. Theophylline per se had effects on neuroeffector transmission opposite to those of adenosine. All effects of adenosine were antagonized effectively or annulled by theophylline in concentrations having little or no effect on rabbit kidney phosphodiesterase activities. Two other compounds, Ro 20-1724 and ZK 62.711, being equally potent or more potent than theophylline as phosphodiesterase inhibitors, failed to antagonize adenosine-mediated inhibition of (-)-NE[3H] release by nerve stimulation. Ro 20-1724 in high concentration (10(-4) M) inhibited the vasoconstrictor response to nerve stimulation, but it had little additional effect on the enhancement by adenosine. These findings suggest that theophylline specifically antagonizes the effects of adenosine on pre- and postjunctional transmission in the kidney. The results also are consistent with the view that endogenous adenosine may play a role as modulator of adrenergic neuroeffector transmission.