Probenecid blocks human P2X7 receptor-induced dye uptake via a pannexin-1 independent mechanism.
Probenecid blocks human P2X7 receptor-induced dye uptake via a pannexin-1 independent mechanism.
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DOI：
10.1371/journal.pone.0093058
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Stokes L
中科院分区：
文献类型：
--
作者：
Bhaskaracharya A;Dao-Ung P;Jalilian I;Spildrejorde M;Skarratt KK;Fuller SJ;Sluyter R;Stokes L
P2 X7是由ATP激活的配体门控离子通道，并显示次级渗透性特征。虽然已经提出了半通道蛋白泛连接蛋白-1的作用，但是次级通透性途径的发展机制目前尚不清楚。在这项研究中，我们研究了泛连接蛋白-1在P2 X7诱导的染料摄取和ATP诱导的人单核细胞分泌IL-1β中的作用。我们没有发现pannexin-1参与转染的HEK-293细胞中P2 X7介导的染料摄取的药理学证据，对于甘珀酸和pannexin-1模拟抑制肽10 Panx 1没有观察到抑制。然而，我们发现丙磺舒抑制P2 X7诱导的阳离子和阴离子染料摄取稳定转染的人P2 X7 HEK-293细胞。计算出阻断人P2 X7 ATP诱导反应的IC 50值为203 μM。丙磺舒还降低了人CD 14+单核细胞的染料摄取和IL-1β分泌，而甘珀酸和10 Panx 1没有显示出抑制作用。膜片钳和钙指示剂实验显示丙磺舒直接阻断人P2 X7受体。
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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影响因子：
7.3
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0709684105
发表时间：
2008-06-10
影响因子：
11.1
作者：
Piccini, Alessandra;Carta, Sonia;Rubartelli, Anna
通讯作者：
Rubartelli, Anna