Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 336, Issue 2, pp 204–210

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

  • Martin J. Lohse
  • Karl-Norbert Klotz
  • Jutta Lindenborn-Fotinos
  • Martin Reddington
  • Ulrich Schwabe
  • Ray A. Olsson
Article

DOI: 10.1007/BF00165806

Cite this article as:
Lohse, M.J., Klotz, KN., Lindenborn-Fotinos, J. et al. Naunyn-Schmiedeberg's Arch Pharmacol (1987) 336: 204. doi:10.1007/BF00165806

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 K1-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 (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 [3H]DPCPX appear superior to those of other agonist and antagonist radioligands for the A1 receptor.

Key words

Adenosine receptorsAdenylate cyclasePhosphodiesteraseXanthinesRadioligands

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)

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • Martin J. Lohse
    • 1
  • Karl-Norbert Klotz
    • 1
  • Jutta Lindenborn-Fotinos
    • 1
  • Martin Reddington
    • 2
  • Ulrich Schwabe
    • 1
  • Ray A. Olsson
    • 3
  1. 1.Pharmakologisches Institut der Universität HeidelbergHeidelbergFederal Republic of Germany
  2. 2.Max-Planck-Institut für PsychiatrieMartinsriedFederal Republic of Germany
  3. 3.Departments of Internal Medicine and BiochemistryUniversity of South FloridaTampaUSA