Pentobarbital Antagonizes the A1 Adenosine Receptor‐Mediated Inhibition of Hippocampal Neurotransmitter Release

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Abstract
Barbiturates have been shown to be competitive antagonists at A1 adenosine receptors in radioligand binding studies. The present study investigates the effects of pentobarbital on the A1 receptor-mediated inhibition of neurotransmitter release from rabbit hippocampal slices. The inhibition of the electrically evoked release of [3H]noradrenaline by the A1 receptor agonist (R)-N6-phenylisopropyladenosine (R-PIA) was antagonized by pentobarbital with an apparent pA2 value of 3.5. Low concentrations of pentobarbital alone altered neither basal nor evoked release of [3H]noradrenaline, whereas 1,000 .mu.M pentobarbital enhanced the basal and reduced the evoked release. In the presence of 8-phenyltheophylline, pentobarbital (200 .mu.M and 1,000 .mu.M) reduced the evoked noradrenaline release. "Pentobarbital also antagonized the inhibition of [3H]acetylcholine release of R-PIA. In contrast to the noradrenaline release model, the evoked release of acetylcholine was enhanced by the presence of pentobarbital (50-500 .mu.M), an effect that was lost in the presence of 8-phenyltheophylline. These results indicate that pentobarbital, in addition to a direct inhibitory action at higher concentrations, has a facilitatory effect on neurotransmitter release by blocking presynaptic A1 adenosine receptors. The possible relevance of these findings for the excitatory effects of barbiturates is discussed.