Pentobarbital antagonizes the A1 adenosine receptor-mediated inhibition
of hippocampal neurotransmitter release
J Neurochem, 49 (1):
189-94 (July 1987)Lohse, M J Brenner, A S Jackisch, R United states Journal of neurochemistry
J Neurochem. 1987 Jul;49(1):189-94..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 3Hnoradrenaline 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
3Hnoradrenaline, 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 3Hacetylcholine
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.