Abstract
Barbiturates in pharmacologically relevant concentrations inhibit
binding of (R)-N6-phenylisopropyl3Hadenosine (3HPIA) to solubilized
A1 adenosine receptors in a concentration-dependent, stereospecific,
and competitive manner. Ki values are similar to those obtained for
membrane-bound receptors and are 31 microM for (+/-)-5-(1,3-dimethyl)-5-ethylbarbituric
acid (+/-)-DMBB and 89 microM for (+/-)-pentobarbital. Kinetic
experiments demonstrate that barbiturates compete directly for the
binding site of the receptor. The inhibition of rat striatal adenylate
cyclase by unlabelled (R)-N6-phenylisopropyladenosine (R)-PIA is
antagonized by barbiturates in the same concentrations that inhibit
radioligand binding. The stimulation of adenylate cyclase via A2
adenosine receptors in membranes from N1E 115 neuroblastoma cells
is antagonized only by 10-30 times higher concentrations of barbiturates.
It is concluded that barbiturates are selective antagonists at the
A1 receptor subtype. In analogy to the excitatory effects of methylxanthines
it is suggested that A1 adenosine receptor antagonism may convey
excitatory properties to barbiturates.
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