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

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...

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Bibliographic Details
Published in:Biochemical pharmacology 2008-12, Vol.76 (12), p.1740-1747
Main Authors: MOORE, Samantha F, MACKENZIE, Amanda B
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - analogs & derivatives
Adenosine Triphosphate - pharmacology
Animals
Biological and medical sciences
Copper - pharmacology
Macrophages - chemistry
Medical sciences
Mice
Pharmacology. Drug treatments
Purinergic P2 Receptor Agonists
Rats
Receptors, Purinergic P2 - drug effects
Receptors, Purinergic P2X7
Recombinant Proteins
Species Specificity
Zinc - pharmacology
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Summary: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.
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2008.09.015