Species and agonist dependent zinc modulation of endogenous and recombinant ATP-gated P2X sub(7) receptors

• Published in: Biochemical pharmacology 2008-12, Vol.76 (12), p.1740-1747
• Main Authors: Moore, Samantha F, MacKenzie, Amanda B
• Format: Article
• Language: English
• ISSN: 0006-2952
• DOI: 10.1016/j.bcp.2008.09.015

Zinc (Zn super(2+)) and copper (Cu super(2+)) are key signalling molecules in the immune system and regulate the activity of many ion channels. Both Zn super(2+) and Cu super(2+) potently inhibit rat P2X sub(7) receptors via a binding site identified by mutagenesis. Here we show that extracellular Cu super(2+) also potently inhibits mouse P2X sub(7) receptors. By contrast, the receptor expression system and agonist strongly influence the action of extracellular Zn super(2+) at mouse P2X sub(7) receptors. Consistent with previous reports, Zn super(2+) inhibits recombinant rat P2X sub(7) receptors. However, recombinant mouse P2X sub(7) receptors are potentiated by Zn super(2+) when activated by ATP super(4-) but inhibited when stimulated with the ATP analogue BzATP super(4-). Endogenous murine macrophage P2X sub(7) receptors are not modulated by Zn super(2+) when stimulated by ATP super(4-) however Zn super(2+) inhibits BzATP super(4-) mediated responses. In summary, these findings provide a fundamental insight into the differential actions of Zn super(2+) and Cu super(2+) between different P2X sub(7) receptor species.