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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.

Author information

1
Sydney Medical School Nepean, University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia.
2
School of Biological Sciences, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia.
3
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.

Abstract

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.

PMID:
24671093
PMCID:
PMC3966854
DOI:
10.1371/journal.pone.0093058
[Indexed for MEDLINE]
Free PMC Article

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