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

Bhaskaracharya, Archana, Dao-Ung, Phuong, Jalilian, Iman, Spildrejorde, Mari, Skarratt, Kristen K., Fuller, Stephen J., Sluyter, Ronald and Stokes, Leanne ORCID: (2014) Probenecid blocks human P2X7 receptor-induced dye uptake via a pannexin-1 independent mechanism. PLoS One, 9 (3). ISSN 1932-6203

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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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Science > Research Groups > Molecular and Tissue Pharmacology
Depositing User: Pure Connector
Date Deposited: 18 Oct 2017 05:08
Last Modified: 03 Aug 2023 13:30
DOI: 10.1371/journal.pone.0093058

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