title: Pentobarbital antagonizes the A1 adenosine receptor-mediated inhibition of hippocampal neurotransmitter release.
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.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D010424:Pentobarbital / Q000494:pharmacology*; D011817:Rabbits; D011983:Receptors, Purinergic / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018377:Neurotransmitter Agents; D011983:Receptors, Purinergic; D013806:Theophylline; C028322:8-phenyltheophylline; D010424:Pentobarbital; D000241:Adenosine; D000109:Acetylcholine; D009638:Norepinephrine