Oxidized ATP. An irreversible inhibitor of the macrophage purinergic P2Z receptor.

Murgia, Marta; Hanau, Stefania; Pizzo, Paola; Rippa, Massimo; Virgilio, Francesco Di

doi:10.1016/s0021-9258(18)53082-9

Cited by 309 publications

(30 citation statements)

References 25 publications

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“…Furthermore, pretreatment with pertussis toxin (PTX) (100 ng/ml) did not affect ATP-induced IL-6 release (Figure 2b). ATP or BzATP (100 mM)induced IL-6 release was inhibited in the presence of periodate-oxidized ATP (oATP), an irreversible inhibitor of P2X 7 receptors (Murgia et al, 1993) (Figure 2c). However, 1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62), the most potent P2X 7 receptors antagonist in the nanomolar range (Gargett and Wiley, 1997), did not inhibit ATP or BzATP (100 mM)-induced IL-6 release (Figure 2d).…”

Section: Resultsmentioning

confidence: 99%

Extracellular ATP Has Stimulatory Effects on the Expression and Release of IL-6 Via Purinergic Receptors in Normal Human Epidermal Keratinocytes

Inoué

Hosoi

Denda

2007

Journal of Investigative Dermatology

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Extracellular ATP regulates proliferation and differentiation, functioning as an important messenger via purinergic (P2) receptors in keratinocytes. In this study, we investigated the effects of ATP on cytokine production in cultured normal human epidermal keratinocytes (NHEKs). Adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), adenosine 5'-O-2-(thio)diphosphate (ADPbetaS), ADP, ATP, and 2', 3'-O-(4-benzoyl-benzoyl) ATP (BzATP) significantly increased the release of IL-6. The P2 antagonists, suramin-, reactive blue 2-, and periodate-oxidized ATP, inhibited ATP-induced IL-6 release, whereas pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, adenosine 3'-phosphate 5'-phosphate, 1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine, and pertussis toxin did not. SQ22563, an adenylate cyclase inhibitor, inhibited ATP-induced IL-6 release. ATPgammaS, ADPbetaS, ATP, and BzATP significantly increased the intracellular cAMP content. Reverse transcription-PCR showed expression of P2Y1, P2Y2, P2Y4, P2Y11, P2Y12, P2Y13, P2X1, P2X4, P2X5, P2X6, and P2X7 receptor subtypes. Additionally, UVB radiation evoked the release of ATP from NHEKs. The release of IL-6 and the expression of IL-6 mRNA were increased after UVB radiation, and these increases were also inhibited by P2 receptor antagonists. These results suggest that cAMP-generating P2Y receptors are likely functional in ATP-induced IL-6 production in NHEKs. Furthermore, in UVB-radiated cells, we note the possibility that P2 receptor antagonists may reduce skin inflammation.

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Section: Resultsmentioning

confidence: 99%

Extracellular ATP Has Stimulatory Effects on the Expression and Release of IL-6 Via Purinergic Receptors in Normal Human Epidermal Keratinocytes

Inoué

Hosoi

Denda

2007

Journal of Investigative Dermatology

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“…Several charged amino acids (Lys64, Lys66, Lys193, Arg294, and Lys311) involved in coordination of the three phosphate groups of ATP and a threonine residue (Thr189) involved in interaction with the adenine moiety are present at the bottom of the ATP-binding pocket of the human P2X7R (Figure 2D). Presence of four lysines in the ATP-binding domain might explain the exquisite sensitivity of P2X7R to blockade by oxidized ATP (Murgia et al, 1993), a widely used di-aldehyde P2X7R inhibitor that forms Schiff bases with un-protonated lysines. Sequence analysis and tertiary structure of the entrance of the ATP-binding pocket show lack of positively charged amino acids and a restricted access, suggesting a rather small volume of the binding cavity and difficult entry for hydrophilic compounds, which might explain why P2X7R has typically low affinity for ATP and for several negatively charged drug-like compounds active at other P2XRs.…”

Section: The P2x7r Structurementioning

confidence: 99%

The P2X7 Receptor in Infection and Inflammation

et al. 2017

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Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known. The P2X7R is a potent stimulant of inflammation and immunity and a promoter of cancer cell growth. This makes P2X7R an appealing target for anti-inflammatory and anti-cancer therapy. However, an in-depth knowledge of its structure and of the associated signal transduction mechanisms is needed for an effective therapeutic development.

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“…Thereafter, cells were exposed to either 5 mM ATP or saline only for 30 minutes to trigger IL-1β release. Some wells were preincubated for 30 minutes with the P2X 7 antagonist oxidized ATP (oATP; 0.3 mM) 16 following LPS stimulation but prior to the addition of ATP. This concentration of oATP has been shown to have no effect on P2Y receptors in the J-774 macrophage cell line.…”

Section: Measurement Of Il-1β β Releasementioning

confidence: 99%

“…This concentration of oATP has been shown to have no effect on P2Y receptors in the J-774 macrophage cell line. 16 Controls consisted of unstimulated (without LPS and ATP) cells maintained in culture media. After incubations, supernatants were removed and centrifuged to remove cell debris, and aliquots were frozen at -20°C until required for quantitation of IL-1β release by enzyme-linked immunosorbent assay (ELISA; Quantikine human IL-1β ELISA kit; R&D Systems, Abingdon, UK).…”

Section: Measurement Of Il-1β β Releasementioning

confidence: 99%

Interleukin-1β Secretion From Cord Blood Mononuclear Cells In Vitro Involves P2X7 Receptor Activation

et al. 2008

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The purinergic receptor P2X(7) is activated by extracellular adenosine 5'-triphosphate (ATP) and promotes the efficient release of interleukin-1 beta. The authors examine protein and molecular expression of the P2X(7) receptor and its ability to stimulate interleukin-1 beta release in cord blood mononuclear cells (CBMCs) from placentae of term nonlaboring and laboring women. They show both mRNA and protein (78 kDa) expression for the P2X( 7) receptor in CBMCs of parturient and nonparturient women. Costimulation of CBMCs in vitro with bacterial endotoxin and ATP resulted in significantly (P < .05) enhanced interleukin-1 beta release in laboring (54.17 +/- 24.78 pg/mL(-1); n = 8) compared with nonlaboring (13.60 +/- 3.20 pg/mL(-1); n = 7) deliveries. Release of interleukin-1 beta in both groups was blocked by preincubation with oxidized ATP, a P2X(7) receptor antagonist. The authors provide evidence for a novel inflammatory pathway in the release of interleukin-1 beta, which may be linked to the onset of labor.

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Oxidized ATP. An irreversible inhibitor of the macrophage purinergic P2Z receptor.

Cited by 309 publications

References 25 publications

Extracellular ATP Has Stimulatory Effects on the Expression and Release of IL-6 Via Purinergic Receptors in Normal Human Epidermal Keratinocytes

Extracellular ATP Has Stimulatory Effects on the Expression and Release of IL-6 Via Purinergic Receptors in Normal Human Epidermal Keratinocytes

The P2X7 Receptor in Infection and Inflammation

Interleukin-1β Secretion From Cord Blood Mononuclear Cells In Vitro Involves P2X7 Receptor Activation

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