Inhibitory Effects of Metals on ATP-Induced Current Through P2X7 Receptor in NG108-15 Cells

Watano, Tomokazu; Matsuoka, Isao; Kimura, Junko

doi:10.1254/jjp.89.296

Cited by 7 publications

(6 citation statements)

References 44 publications

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“…Potent inhibition of P2X7R current by Cu 2ϩ was reported before (29) and shown to be noncompetitive with ATP (36). However, we note two differences between the effect of Cu 2ϩ in model systems and native cells.…”

Section: P2rs In Parotid Glandsupporting

confidence: 62%

Cell-specific Behavior of P2X7 Receptors in Mouse Parotid Acinar and Duct Cells

Luo

Zeng

et al. 2003

Journal of Biological Chemistry

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Rather, disassembly or solidification of the actin cytoskeleton prior to incubation with ATP prevented channel assembly. Remarkably, after completion of the slow activation, manipulation of the actin cytoskeleton no longer affected gating by ATP. Accordingly, manipulation of the actin cytoskeleton had no effect on P2X7R gating by ATP in duct cells. We concluded that P2X7Rs are not active in resting acinar cells. On exposure to ATP, P2X7Rs are assembled into functional channels with the aid of the actin cytoskeleton. Once assembled, P2X7Rs are subject to rapid gating by ATP. Duct cell P2X7Rs are preassembled and therefore continually subject to rapid gating by ATP. This cell-specific behavior may reflect the specific function of P2X7Rs in the two cell types.

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Section: P2rs In Parotid Glandsupporting

confidence: 62%

Cell-specific Behavior of P2X7 Receptors in Mouse Parotid Acinar and Duct Cells

Luo

Zeng

et al. 2003

Journal of Biological Chemistry

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“…Alkalinization of the medium or removal of Mg 2+ and Ca 2+ increases the apparent affinity of ATP and BzATP for the native and recombinant P2X 7 receptor [ 11 , 28 , 29 ]. Metal ions such as Cu 2+ , Ni 2+ , Cd 2+ , Zn 2+ , Co 2+ inhibit P2X 7 evoked currents [ 30 , 31 ]. The widely used calmodulin antagonist calmidazolium, inhibits BzATP-induced currents in HEK293 cells stably expressing the rat P2X 7 receptor while, it has no effect on YO-PRO-1 uptake.…”

Section: P2x 7 : From An Elusive Receptor To An Atmentioning

confidence: 99%

P2X7 receptor: Death or life?

Adinolfi

Pizzirani

Idzko

et al. 2005

Purinergic Signalling

121

123

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The P2X 7 plasma membrane receptor is an intriguing molecule that is endowed with the ability to kill cells, as well as to activate many responses and even stimulate proliferation. Here, the authors give an overview on the multiplicity and complexity of P2X 7 -mediated responses, discussing recent information on this receptor. Particular attention has been paid to early and late signs of apoptosis and necrosis linked to activation of the receptor and to the emerging field of P2X 7 function in carcinogenesis.P2X 7 : From an elusive receptor to an ATP-gated channel/pore The P2X 7 receptor (P2X 7 R) for extracellular ATP is expressed by a variety of cell types as different as neurons, macrophages, dendritic and microglial cells, fibroblasts, lymphocytes, and endothelial cells. At least a subpopulation of human osteoblasts also express P2X 7 [1]. Expression of the receptor has been demonstrated in human fibroblasts [2,3] and epithelia from the human bladder [4,5], human and rat uterus [6,7], male genital organs of the rats [8], human fetal keratinocytes [9] and mouse parotid acinar and duct cells [10].Although interest in this molecule has increased exponentially since the late 1990s, initial observations on its peculiar biochemical properties go back to the 1970s, when Cockcroft and Gomperts reported that extracellular ATP caused degranulation and striking morphological changes in rat mast cells [11]. These authors also hypothesized that cell responses triggered by ATP, such as histamine secretion and phosphatidyl inositol formation, were due to activation of an as yet unknown receptor (the FATP receptor_) activated by the fully dissociated ATP form (ATP 4j ) [12]. Based on its intriguing ability to cause a reversible permeabilization of the plasma membrane, this receptor was also referred to as the Fpermeabilizing ATP receptor_ later named P2Z [13]. P2Z was described not only in rat mast cells but also in mouse macrophages [14,15]. Following these early observations, the peculiar pharmacological and biochemical properties of the P2Z receptor were recognized in many other cells such as human macrophages, human B lymphocytes, mouse microglial cells, mouse and human monocyte-derived dendritic cells.The permeabilizing ATP receptor was cloned in 1996 from a rat brain library and named P2X 7 for its homology with the other P2X receptors [16]. P2X 7 is a 595 AA protein with a predicted structure comprising two transmembrane domains and a bulky extracellular cysteine rich region, with conserved lysine and glycine residues and several potential N-linked glycosylation sites, followed by a long stretch (from Phe 188 to Val 321 ) forming six putative antiparallel b sheets. The amino and carboxyl-terminal domains are both cytoplasmic. Similarities have been found between the b sheets region and the catalytic domains of class II aminoacylYtRNA synthetases [17]. These b sheets are likely to include residues comprising the ATP-binding site, since substitution of two aminoacids comprised in this region, Lys 193 and Lys 311...

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“…In contrast to other P2X receptors, where divalent metals may either potentiate or inhibit receptor activity, the P2X 7 receptor is inhibited by copper and zinc (Virginio et al. 1997; Watano et al. 2002;Coddou et al.…”

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confidence: 98%

Differential role of extracellular histidines in copper, zinc, magnesium and proton modulation of the P2X₇ purinergic receptor

Acuña-Castillo

Coddou²,

Bull

et al. 2007

Journal of Neurochemistry

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The P2X 7 receptor is a non-selective cationic channel activated by extracellular ATP, belonging to the P2X receptor family. To assess the role of extracellular histidines on the allosteric modulation of the rat P2X 7 receptor by divalent metals (copper, zinc and magnesium) and protons, these amino acid residues were singly substituted for corresponding alanines. Wild-type and mutated receptors were injected to Xenopus laevis oocytes; metal-related effects were evaluated by the two-electrode voltage-clamp technique. Copper inhibited the ATP-gated currents with a median inhibitory concentration of 4.4 ± 1.0 lmol/L. The inhibition was noncompetitive and time-dependent; copper was 60-fold more potent than zinc. The mutant H267A, resulted in a copper resistant receptor; mutants H201A and H130A were less sensitive to copper inhibition (p < 0.05). The rest of the mutants examined, H62A, H85A, and H219A, conserved the copper-induced inhibition. Only mutants H267A and H219Awere less sensitive to the modulator action of zinc. Moreover, the magnesium-induced inhibition was abolished exclusively on the H130A and H201A mutants, suggesting that this metal may act at a novel cationic modulator site. Media acidification inhibited the ATP-gated current 87 ± 3%; out of the six mutants examined, only H130A was significantly less sensitive to the change in pH, suggesting that His-130 could be involved as a pH sensor. In conclusion, while His-267 is critically involved in the copper or zinc allosteric modulation, the magnesium inhibitory effects is related to His-130 and His-201, His-130 is involved in proton sensing, highlighting the role of defined extracellular histidines in rat P2X 7 receptor allosteric modulation.

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Inhibitory Effects of Metals on ATP-Induced Current Through P2X7 Receptor in NG108-15 Cells

Cited by 7 publications

References 44 publications

Cell-specific Behavior of P2X7 Receptors in Mouse Parotid Acinar and Duct Cells

Cell-specific Behavior of P2X7 Receptors in Mouse Parotid Acinar and Duct Cells

P2X7 receptor: Death or life?

Differential role of extracellular histidines in copper, zinc, magnesium and proton modulation of the P2X₇ purinergic receptor

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Inhibitory Effects of Metals on ATP-Induced Current Through P2X7 Receptor in NG108-15 Cells

Cited by 7 publications

References 44 publications

Cell-specific Behavior of P2X7 Receptors in Mouse Parotid Acinar and Duct Cells

Cell-specific Behavior of P2X7 Receptors in Mouse Parotid Acinar and Duct Cells

P2X7 receptor: Death or life?

Differential role of extracellular histidines in copper, zinc, magnesium and proton modulation of the P2X7 purinergic receptor

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Differential role of extracellular histidines in copper, zinc, magnesium and proton modulation of the P2X₇ purinergic receptor