Abstract
The properties of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as an
antagonist ligand for A1 adenosine receptors were examined and compared
with other radioligands for this receptor. DPCPX competitively antagonized
both the inhibition of adenylate cyclase activity via A1 adenosine
receptors and the stimulation via A2 adenosine receptors. The Ki-values
of this antagonism were 0.45 nM at the A1 receptor of rat fat cells,
and 330 nM at the A2 receptor of human platelets, giving a more than
700-fold A1-selectivity. A similar A1-selectivity was determined
in radioligand binding studies. Even at high concentrations, DPCPX
did not significantly inhibit the soluble cAMP-phosphodiesterase
activity of human platelets. 3HDPCPX (105 Ci/mmol) bound in a saturable
manner with high affinity to A1 receptors in membranes of bovine
brain and heart, and rat brain and fat cells (KD-values 50-190 pM).
Its nonspecific binding was about 1% of total at KD, except in bovine
myocardial membranes (about 10%). Binding studies with bovine myocardial
membranes allowed the analysis of both the high and low agonist affinity
states of this receptor in a tissue with low receptor density. The
binding properties of 3HDPCPX appear superior to those of other
agonist and antagonist radioligands for the A1 receptor.
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