Abstract
The effects of barbiturates on radioligand binding to inhibitory Ri
adenosine receptors of rat brain membranes were investigated. Binding
of the adenosine receptor agonist (-)N6-phenylisopropyl3Hadenosine
and the antagonist 1,3-diethyl-8-3Hphenylxanthine was inhibited
by several barbiturates. This inhibition was concentration-dependent
and occurred in the range of pharmacologically effective concentrations.
Pentobarbital was the most potent of the barbiturates tested with
a Ki of 92 mumol/l. The (+)isomers of hexobarbital and mephobarbital
were more potent than the respective (-)isomers. Barbituric acid
itself did not displace either radioligand in concentrations up to
1 mmol/l. The inhibitory effect of pentobarbital was reversed by
a single wash of membranes preincubated with the barbiturate. The
presence of pentobarbital caused a decrease of the affinity of the
receptor for the antagonist radioligand but did not alter the number
of binding sites, suggesting a competitive antagonism. The effects
of pentobarbital on radioligand binding to the receptor were not
changed by the presence of picrotoxinin nor by the absence of chloride
ions. This indicates that they are not mediated via the picrotoxinin
binding site. The barbiturates could not be classified as either
agonists or antagonists at the Ri adenosine receptor. The presence
of GTP did not influence the inhibition of radioligand binding by
pentobarbital; this is also observed for antagonists, whereas the
affinity of agonists is markedly reduced by GTP. Binding of antagonists
to the receptor is enthalpy-driven; the interaction of pentobarbital
with the receptor was entropy-driven and the same was true for agonists.(ABSTRACT
TRUNCATED AT 250 WORDS)
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