Dissecting individual current components of co-expressed human P2X1 and P2X7 receptors

Curr Top Med Chem. 2004;4(16):1719-30. doi: 10.2174/1568026043387160.

Abstract

Purinergic P2X(1) and P2X(7) receptors are co-expressed in several cell types such as lymphocytes or epithelial cells. Here we examined whether these two P2X subtypes interact with each other in a manner that results in a mutual alteration of their electrophysiologic behaviour. Furthermore, since specific pharmacological tools are needed to assign distinct effects to a particular receptor subtype in native cells, we assessed a series of compounds for their capacity to separate individual current components in cells that co-expressed both receptor subtypes. In Xenopus oocytes, co-expression neither changed the time courses of activation, desensitization and deactivation nor recovery from desensitization when compared to oocytes that express either hP2X(1) or hP2X(7) receptors alone. A selective activation of hP2X(7) receptors was achieved with benzoyl-benzoyl-ATP, which did not activate P2X(1) receptor currents. P2X(7) receptors could also be selectively activated by ATP when co-applied with 1 microM NF449, a suramin derivative, which is 100,000 fold more potent in blocking P2X(1) than P2X(7) receptors. alphabeta-methylene-ATP, a reportedly hP2X(1) receptor-specific agonist, as well as oxidized-ATP, brilliant blue or KN62, reported hP2X(7) receptor antagonists, were found to be ineffective in separating hP2X(1) receptor current from the P2X(7) current. The best way for a selective activation of the hP2X(1) receptor component in cells co-expressing the P2X(7) receptor is the application of low concentrations of ATP (< 1 microM) or the addition of Mg2+ when using higher concentrations of ATP.

Publication types

  • Comparative Study

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Benzenesulfonates / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Magnesium / pharmacology
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Purinergic P2 Receptor Agonists
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2 / physiology*
  • Receptors, Purinergic P2X
  • Receptors, Purinergic P2X7
  • Suramin / analogs & derivatives
  • Suramin / pharmacology
  • Time Factors
  • Xenopus laevis

Substances

  • Benzenesulfonates
  • P2RX7 protein, human
  • Purinergic P2 Receptor Agonists
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X
  • Receptors, Purinergic P2X7
  • Suramin
  • KN 62
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Adenosine Triphosphate
  • brilliant blue
  • Magnesium