Selectivity of diadenosine polyphosphates for rat P2X receptor subunits

Eur J Pharmacol. 1999 Feb 12;367(1):119-23. doi: 10.1016/s0014-2999(98)00976-5.

Abstract

The pharmacological activity of diadenosine polyphosphates was investigated at three recombinant P2X receptors (rat P2X1, rat P2X3, rat P2X4) expressed in Xenopus oocytes and studied under voltage-clamp conditions. For the rat P2X1 receptor, only P1,P6-diadenosine hexaphosphate (Ap6A) was a full agonist yet 2-3 folds less potent than ATP. At rat P2X3, P1,p4-diadenosine tetraphosphate (Ap4A), P1,P5-diadenosine pentaphosphate (Ap5A) and Ap6A were full agonists and more potent than ATP. Ap4A alone was equipotent with ATP at rat P2X4, but only as a partial agonist. Compared to known data for rat P2X2 and human P2X1 receptors, our findings contrast with rat P2X2 where only Ap4A is a full agonist although four folds less potent than ATP. At rat and human orthologues of P2X1, Ap5A was a partial agonist with similar potency. These data provide a useful basis for selective agonists of P2X receptor subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Binding, Competitive / drug effects
  • Dinucleoside Phosphates / metabolism
  • Dinucleoside Phosphates / pharmacology*
  • Dose-Response Relationship, Drug
  • Membrane Potentials / drug effects
  • Oocytes / drug effects
  • Oocytes / physiology
  • Purinergic P2 Receptor Agonists
  • RNA, Messenger / administration & dosage
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X
  • Receptors, Purinergic P2X3
  • Receptors, Purinergic P2X4
  • Xenopus

Substances

  • Adenine Nucleotides
  • Dinucleoside Phosphates
  • P2RX3 protein, human
  • P2RX4 protein, human
  • P2rx3 protein, rat
  • P2rx4 protein, rat
  • Purinergic P2 Receptor Agonists
  • RNA, Messenger
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X
  • Receptors, Purinergic P2X3
  • Receptors, Purinergic P2X4
  • P(1),P(5)-di(adenosine-5'-)pentaphosphate
  • diadenosine tetraphosphate
  • diadenosine triphosphate
  • diadenosine 5',5''''-P1,P6-hexaphosphate
  • Adenosine Triphosphate