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Pentobarbital Antagonizes the A 1 Adenosine Receptor‐Mediated Inhibition of Hippocampal Neurotransmitter Release
Author(s) -
Lohse Martini,
Brenner Angelika S.,
Jackisch Rolf
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb03413.x
Subject(s) - pentobarbital , neurotransmitter , acetylcholine , adenosine , chemistry , pharmacology , endocrinology , medicine , inhibitory postsynaptic potential , adenosine receptor , agonist , receptor , biology , biochemistry
Barbiturates have been shown to be competitive antagonists at A 1 adenosine receptors in radioligand binding studies. The present study investigates the effects of pentobarbital on the A 1 receptor‐mediated inhibition of neuro‐transmitter release from rabbit hippocampal slices. The inhibition of the electrically evoked release of [ 3 H]noracrenaline by the AI receptor agonist ( R )‐ N 6 ‐phenylisopro‐pyladenosine (R‐PIA) was antagonized by pentobarbital with an apparent pA 2 value of 3.5. Low concentrations of pentobarbital alone altered neither basal nor evoked release of [ 3 H]noradrenaline, whereas 1,000 μM pentobarbital enhanced the basal and reduced the evoked release. In the presence of 8‐phenyltheophylline, pentobarbital (200 μM and 1,000 μM) reduced the evoked noradrenaline release. Pentobarbital also antagonized the inhibition of [ 3 H]acetyl‐choline 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 μM) , 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 faci‐litatory effect on neurotransmitter release by blocking pre‐synaptic A 1 adenosine receptors. The possible relevance of these findings for the excitatory effects of barbiturates is discussed.