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 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.
Moore
Samantha F
SF
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Mackenzie
Amanda B
AB
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003300:Copper / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D058486:Receptors, Purinergic P2X7; D011994:Recombinant Proteins; D013045:Species Specificity; D015032:Zinc / Q000494:pharmacology*
C546469:P2rx7 protein, mouse; C546470:P2rx7 protein, rat; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D011994:Recombinant Proteins; D003300:Copper; D000255:Adenosine Triphosphate; D015032:Zinc