P2Z Purinoceptors

Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptor

“…Concentration–inhibition curves were obtained for the actions of 10 panx1 in inhibiting P2X 7 ‐mediated dye uptake and in inhibiting panx‐1 mediated currents in panx‐1 overexpressing cells; in both assays a similar half‐maximal inhibitory concentration was obtained (30–50 μM; Supplementary Figure 2A). These concentrations are within the range (50–1000 μM) typically seen to be effective in other systems where peptide‐mimetic inhibitors are commonly used (Hickman et al , 1996; Gudipaty et al , 2003; Mariathasan et al , 2004; Elliott et al , 2005). Steady‐state inhibition by an IC 50 concentration of 10 panx1 required 10–20 min with washout being accomplished within 15–25 min ( n =4).…”

“…Connexins are a multigene superfamily of proteins well known to form gap junctions; gap junctions are formed between cells by docking of connexin hemichannels, which are thought to exist as undocked oligomers prior to junctional formation (Spray et al , 2002; Dhein, 2004; Griffith et al , 2004). However, several previous studies have ruled out involvement of connexins in P2X 7 R activation and dye uptake (Steinberg and Di Virgilio, 1991; Hickman et al , 1996). Pannexins are a recently identified three‐membered family (Panx1, Panx2, Panx3) of mammalian proteins that have low sequence homology, but general structural similarity, to a family of non‐mammalian proteins (innexins) that form gap junctions in invertebrate tissue (Panchin, 2005; Barbe et al , 2006).…”

Pannexin1 is part of the pore forming unit of the P2X7 receptor death complex

“…Expression of cloned P2X 7 R in mammalian cells led to uptake of moderately large fluorescent dyes upon exposure to P2X receptor agonists [4], as had been reported for ATP activation of the permeabilizing pore (formerly known as the P2Z receptor) [18–21]. However, this property has not yet been observed in P2X 7 ‐RNA injected Xenopus oocytes [6,22], although when macrophage mRNA is co‐injected, oocyte permeabilization occurs [7].…”

P2 Receptors for Extracellular Nucleotides in the Central Nervous System: Role of P2X7 and P2Y2 Receptor Interactions in Neuroinflammation

“…Stimulation of the P2X7R regulates the gating of non-selective cation channels, mitochondrial and plasma membrane depolarization, the formation of plasma membrane pores, plasma membrane blebbing, and the production of reactive oxygen species (ROS), responses ultimately leading to cell death (Erb et al , 1990; Schulze-Lohoff et al , 1998; Morelli et al , 2003; Verhoef et al , 2003; Wang et al , 2004; Adinolfi et al , 2005; Lister et al , 2007; Roger et al , 2008; Bours et al , 2011). P2X7R activity is dramatically potentiated by decreasing the divalent cation concentration, indicating that ATP 4− may be the active ligand (Steinberg and Silverstein, 1987; Weisman et al , 1989; Hickman et al , 1996). P2X7Rs have been shown to mediate the release of neurotransmitters, e.g.…”