Adenosine: An endogenous modulator of hippocampal noradrenaline release

Abstract

In slices of hippocampus from the rabbit, preincubated with [ 3H]noradrenaline and then continuously superfused, the modulation of the release of noradrenaline by adenosine receptors was studied. Electrical field stimulation of the slices elicited a release of [ 3H]noradrenaline which was inhibited in a concentration-dependent manner by various adenosine receptor agonists. From the order of potency: cyclohexyladenosine > (−)phenylisopropyladenosine [(−)PIA] > 5′- N-ethylcarboxamide-adenosine (NECA) > 2-chloro-adenosine > adenosine (+)phenylisopropyladenosine > ATP, the inhibitory adenosine receptor was classified as A 1- (R i-) receptor. The effect of the agonists was strongly reduced by adenosine receptor antagonists, the methylxanthines. A role for endogenous adenosine in the modulation of hippocampal noradrenaline release is supported by these findings: (1) that blockade of adenosine receptors by methylxanthines, especially by 8-phenyltheophylline, increased, whereas (2) inhibition of the uptake of adenosine decreased the evoked release of noradrenaline and (3) that deamination of endogenous extracellular adenosine by addition of adenosine deaminease to the medium enhanced the evoked transmitter release. Inhibitors of endogenous adenosine deaminase and 5'-nucleotidase were without effect. It is concluded that release of noradrenaline in the hippocampus is inhibited at the level of the noradrenergic neve terminals by endogenous adenosine via A 1 (or R i) receptors.