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PLoS One. 2014 Mar 26;9(3):e93058. doi: 10.1371/journal.pone.0093058. eCollection 2014.

Probenecid blocks human P2X7 receptor-induced dye uptake via a pannexin-1 independent mechanism.

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Sydney Medical School Nepean, University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia.
School of Biological Sciences, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia.
Sydney Medical School Nepean, University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia; Health Innovations Research Institute, School of Medical Sciences, RMIT University, Bundoora, Melbourne, Victoria, Australia.


P2X7 is a ligand-gated ion channel which is activated by ATP and displays secondary permeability characteristics. The mechanism of development of the secondary permeability pathway is currently unclear, although a role for the hemichannel protein pannexin-1 has been suggested. In this study we investigated the role of pannexin-1 in P2X7-induced dye uptake and ATP-induced IL-1β secretion from human monocytes. We found no pharmacological evidence for involvement of pannexin-1 in P2X7-mediated dye uptake in transfected HEK-293 cells with no inhibition seen for carbenoxolone and the pannexin-1 mimetic inhibitory peptide, 10Panx1. However, we found that probenecid inhibited P2X7-induced cationic and anionic dye uptake in stably transfected human P2X7 HEK-293 cells. An IC50 value of 203 μM was calculated for blockade of ATP-induced responses at human P2X7. Probenecid also reduced dye uptake and IL-1β secretion from human CD14+ monocytes whereas carbenoxolone and 10Panx1 showed no inhibitory effect. Patch clamp and calcium indicator experiments revealed that probenecid directly blocks the human P2X7 receptor.

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