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

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Summary

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 K 1-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 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. [3H]DPCPX (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 (K D-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 [3H]DPCPX appear superior to those of other agonist and antagonist radioligands for the A1 receptor.

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Abbreviations

CHA:

N6-cyclohexyladenosine

DPX:

1,3-diethyl-8-phenylxanthine

HPIA:

N6-p-hydroxyphenylisopropyladenosine

NECA,:

′-N-ethylcarboxamidoadenosine

PIA:

N6-phenylisopro-pyladenosine

XAC (“xanthine amine congener”):

8-{4-[([{(2aminoethyl)amino}carbonyl]methyl)oxy]phenyl-1,3-dipropyl-xanthine. 8-Cyclopentyl-1,3-dipropylxanthine is abbreviated DPCPX (from 1,3-dipropyl-8-cyclopentylxanthine)

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität Heidelberg, Im Neuenheimer Feld 366, D-6900, Heidelberg, Federal Republic of Germany

    Martin J. Lohse, Karl-Norbert Klotz, Jutta Lindenborn-Fotinos & Ulrich Schwabe

  2. Max-Planck-Institut für Psychiatrie, D-8033, Martinsried, Federal Republic of Germany

    Martin Reddington

  3. Departments of Internal Medicine and Biochemistry, University of South Florida, 33612, Tampa, FL, USA

    Ray A. Olsson

Authors
  1. Martin J. Lohse
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  2. Karl-Norbert Klotz
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  3. Jutta Lindenborn-Fotinos
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  4. Martin Reddington
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  5. Ulrich Schwabe
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  6. Ray A. Olsson
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Lohse, M.J., Klotz, KN., Lindenborn-Fotinos, J. et al. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) — a selective high affinity antagonist radioligand for A1 adenosine receptors. Naunyn-Schmiedeberg's Arch Pharmacol 336, 204–210 (1987). https://doi.org/10.1007/BF00165806

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  • DOI: https://doi.org/10.1007/BF00165806

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