Pentobarbital Antagonizes the A1 Adenosine Receptor-Mediated Inhibition of Hippocampal Neurotransmitter Release |
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Authors: | Martini Lohse Angelika S Brenner Rolf Jackisch |
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Institution: | Pharmakologisches Institut der Universität Heidelberg, Heidelberg;Pharmakologisches Institut der Universitdt Freiburg, Freiburg, F.R.G. |
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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 microM pentobarbital enhanced the basal and reduced the evoked release. In the presence of 8-phenyltheophylline, pentobarbital (200 microM and 1,000 microM) reduced the evoked noradrenaline release. Pentobarbital also antagonized the inhibition of 3H]acetylcholine release by R-PIA. In contrast to the noradrenaline release model, the evoked release of acetylcholine was enhanced by the presence of pentobarbital (50-500 microM), 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. |
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Keywords: | Hippocampus Noradrenaline release Acetylcholine release A1 adenosine receptor Barbiturates |
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