Species and agonist dependent zinc modulation of endogenous and recombinant ATP-gated P2X7 receptors

Samantha F Moore, Amanda B Mackenzie

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)

Abstract

Zinc (Zn2+) and copper (Cu2+) are key signalling molecules in the immune system and regulate the activity of many ion channels. Both Zn2+ and Cu2+ potently inhibit rat P2X7 receptors via a binding site identified by mutagenesis. Here we show that extracellular Cu2+ also potently inhibits mouse P2X7 receptors. By contrast, the receptor expression system and agonist strongly influence the action of extracellular Zn2+ at mouse P2X7 receptors. Consistent with previous reports, Zn2+ inhibits recombinant rat P2X7 receptors. However, recombinant mouse P2X7 receptors are potentiated by Zn2+ when activated by ATP4- but inhibited when stimulated with the ATP analogue BzATP4-. Endogenous murine macrophage P2X7 receptors are not modulated by Zn2+ when stimulated by ATP4- however Zn2+ inhibits BzATP4- mediated responses. In summary, these findings provide a fundamental insight into the differential actions of Zn2+ and Cu2+ between different P2X7 receptor species.
Original languageEnglish
Pages (from-to)1740-7
Number of pages8
JournalBiochemical Pharmacology
Volume76
Issue number12
DOIs
Publication statusPublished - 15 Dec 2008

Keywords

  • Rats
  • Macrophages
  • Animals
  • Receptors, Purinergic P2X7
  • Purinergic P2 Receptor Agonists
  • Recombinant Proteins
  • Receptors, Purinergic P2
  • Zinc
  • Mice
  • Copper
  • Adenosine Triphosphate
  • Species Specificity

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