8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) — a selective high affinity antagonist radioligand for A1 adenosine receptors

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作者：

MJ Lohse，KN Klotz，J Lindenborn-Fotinos，M Reddington，U Schwabe，RA Olsson

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摘要：

The properties of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as an antagonist ligand for A 1 adenosine receptors were examined and compared with other radioligands for this receptor. DPCPX competitively antagonized both the inhibition of adenylate cyclase activity via A 1 adenosine receptors and the stimulation via A 2 adenosine receptors. The K 1 -values of this antagonism were 0.45 nM at the A 1 receptor of rat fat cells, and 330 nM at the A 2 receptor of human platelets, giving a more than 700-fold A 1 -selectivity. A similar Al-selectivity was determined in radioligand binding studies. Even at high concentrations, DPCPX did not significantly inhibit the soluble cAMP-phosphodiesterase activity of human platelets. [ 3 H]DPCPX (105 Ci/mmol) bound in a saturable manner with high affinity to A 1 receptors in membranes of bovine brain and heart, and rat brain and fat cells ( K D -values 50–190 pM). Its nonspecific binding was about 1 % of total at K D, 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 [ 3 H]DPCPX appear superior to those of other agonist and antagonist radioligands for the A 1 receptor.

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关键词：

Adenosine receptors Adenylate cyclase Phosphodiesterase Xanthines Radioligands

DOI：

10.1007/BF00165806

被引量：

837

年份：

1987