CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation

Pupovac, A, Stokes, L and Sluyter, R 2013, 'CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation', Purinergic Signalling, vol. 9, no. 4, pp. 609-619.


Document type: Journal Article
Collection: Journal Articles

Title CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation
Author(s) Pupovac, A
Stokes, L
Sluyter, R
Year 2013
Journal name Purinergic Signalling
Volume number 9
Issue number 4
Start page 609
End page 619
Total pages 11
Publisher Springer
Abstract The P2X7 receptor is a trimeric ATP-gated cation channel important in health and disease. We have observed that the specific phospholipase D (PLD)1 antagonist, CAY10593 impairs P2X7-induced shedding of the 'low affinity' IgE receptor, CD23. The current study investigated the mode of action of this compound on P2X7 activation. Measurements of ATP-induced ethidium+ uptake revealed that CAY10593 impaired P2X7-induced pore formation in human RPMI 8226 B cells, P2X7-transfected HEK-293 cells and peripheral blood mononuclear cells. Concentration response curves demonstrated that CAY10593 impaired P2X7-induced pore formation in RPMI 8226 cells more potently than the PLD2 antagonist CAY10594 and the non-specific PLD antagonist halopemide. Electrophysiology measurements demonstrated that CAY10593 also inhibited P2X7-induced inward currents. Notably, RT-PCR demonstrated that PLD1 was absent in RPMI 8226 cells, while choline-Cl medium or 1-butanol, which block PLD stimulation and signalling respectively did not impair P2X7 activation in these cells. This data indicates that CAY10593 impairs human P2X7 independently of PLD1 stimulation and highlights the importance of ensuring that compounds used in signalling studies downstream of P2X7 activation do not affect the receptor itself.
Subject Basic Pharmacology
Cell Physiology
Keyword(s) B cell
CD23
Monocyte
P2X7 receptor
Phospholipase D
T cell
DOI - identifier 10.1007/s11302-013-9371-6
Copyright notice © 2013 Springer
ISSN 1573-9538
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
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