Comparative studies on the affinities of ATP derivatives for P2X‐purinoceptors in rat urinary bladder

Xuenong Bo, Bilha Fischer, Michel Maillard, Kenneth A. Jacobson, Geoffrey Burnstock

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62 Scopus citations


Radioligand binding assays have been used to determine the affinities of a series of ATP derivatives with modifications of the polyphosphate chain, adenine and ribose moieties of the ATP molecule for [3H]‐α,β‐methylene ATP ([3H]‐α,β‐MeATP) binding sites in rat urinary bladder. The replacement of the bridging oxygen in the triphosphate chain of ATP (pIC50 = 5.58) with a methylene or imido group markedly increased the affinity (691 fold in IC50 values for β,γ‐imidoATP, 15 fold for β,γ‐methylene ATP), and the replacement of an ionized oxygen on the γ‐phosphate with a sulphur (ATPγS) also led to increased affinity (5623 fold in IC50 values). Modifications at N6, N1, and C‐8 positions on the purine base usually reduced the affinity of ATP (a decrease of 2.8 fold in IC50 values for N6‐methylATP and 8.9 fold for 8‐bromo ATP), while the attachment of an alkylthio group to the C‐2 position greatly increased the affinity for P2X‐purinoceptors (from 3.5 to 98 fold increase in IC50 values). Replacement of the 3′‐hydroxyl group on the ribose with substituted amino or acylamino groups produced more potent P2X‐purinoceptor agonists (an increase of 447 fold in IC50 values for 3′‐deoxy‐3′‐benzylamino ATP and 28 fold for 3′‐deoxy‐3′‐(4‐hydroxyphenylpropionyl)amino ATP. Diadenosine polyphosphates (Ap[n]A) were also shown to displace the [3H]‐α,β‐MeATP binding. The rank order of potency was Ap6A > Ap5A > Ap4A >> Ap3A >> Ap2A. Suramin, PPADS, and reactive blue 2 could competitively displace the binding of [3H]‐α,β‐MeATP to P2X‐purinoceptors, with pIC50 values of 6.26, 5.35, and 6.22, respectively. 1994 British Pharmacological Society

Original languageEnglish
Pages (from-to)1151-1159
Number of pages9
JournalBritish Journal of Pharmacology
Issue number4
StatePublished - Aug 1994
Externally publishedYes


  • ATP derivatives
  • P‐purinoceptors
  • [H]‐α,β‐methylene ATP
  • radioligand binding assay
  • reactive blue 2
  • suramin
  • urinary bladder


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