A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP

Nature ◽  
1994 ◽  
Vol 371 (6497) ◽  
pp. 516-519 ◽  
Author(s):  
Soledad Valera ◽  
Nicolas Hussy ◽  
Richard J. Evans ◽  
Nadia Adami ◽  
R. Alan North ◽  
...  
Keyword(s):  
Ion Channel ◽  
Extracellular Atp ◽  
P2x Receptor ◽  
New Class

scholarly journals New Role for ATP P2X1 Receptors in the Control of Neutrophil Apoptosis and Respiratory Burst Activity.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1647-1647
Author(s):  
Celine Faccinetto ◽  
Christelle Lecut ◽  
Roland Greimers ◽  
Vincent Bours ◽  
Cecile Oury
Keyword(s):  
Respiratory Burst ◽  
Human Peripheral Blood ◽  
P2x Receptors ◽  
Extracellular Atp ◽  
Mononuclear Phagocytes ◽  
P2x Receptor ◽  
Protein Synthesis Inhibitor ◽  
Receptor Subtypes ◽  
Neutrophil Apoptosis ◽  
Tnf Α

Abstract P2X receptors are membrane non-selective cation channels that open in response to the binding of extracellular ATP. Seven genes encode P2X receptor subunits (P2X1–7) in vertebrates. Channels form homo- or hetero-multimers of several subunits that are highly permeable to Ca2+. P2X receptors are widely distributed. In recent years, increasing attention has been paid to extracellular ATP as a candidate danger signal locally released at the inception of inflammation. One of the most striking features of ATP is its ability to promote P2X7 receptor-mediated massive release of mature IL-1β from LPS-primed mononuclear phagocytes. On neutrophils, ATP rises intracellular Ca2+ concentrations, contributes to degranulation, adhesion, oxidative burst and delays apoptosis, events that may partly depend on the G-protein coupled P2Y2 receptor and on P2X7. In the present work, RT-PCR, Western blotting and immunofluorescence experiments reveal that neutrophils also express P2X1 and P2X5 receptor subtypes. A microarray analysis indicates that a 3-hour treatment of human peripheral blood neutrophils with the selective P2X1 and P2X1/5 receptor agonist, a,β-meATP, changes the expression of genes mainly involved in the control of cell fate. Accordingly, this agonist causes an increase of phosphatidylserine exposure on neutrophil membranes, maximally occurring after 3 hours and lasting until 18 hours of culture. In the presence of the protein synthesis inhibitor cycloheximide, a,β -meATP promotes caspase-3-dependent neutrophil apoptosis after 3 hours, which is correlated with highly reduced Fcγ RIII (CD16) membrane expression. In addition, a 1 min pretreatment of neutrophils with a,β -meATP potently increases tumor necrosis factor-a (TNF-α )-driven priming (30 min) of the respiratory burst induced by the bacterially derived peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). Furthermore, a,β -meATP produces L-selectin (CD62L) shedding by its own and in an additive manner with TNF-α . This agonist also induces rapid and reversible phosphorylation of the survival kinases ERK (starting after 2 min) and Akt (15 min) as well as phosphorylation and degradation (after 2 min) of I-κ Bα , an inhibitor of the anti-apoptotic transcription factor NF-κ B. Hence, neutrophil P2X1 receptors might have a dual role in inflammation; they would both contribute to neutrophil activation and promote cell death of neutrophils that have reached the end of their useful life span. Activation of P2X1 receptors by extracellular ATP may thus represent novel regulatory mechanisms that govern neutrophil function.

Cyclic Nucleotide Gated Ion Channel 6 is involved in extracellular ATP signaling and plant immunity

2021 ◽  
Author(s):  
Ha N. Duong ◽  
Sung‐Hwan Cho ◽  
Limin Wang ◽  
An Q. Pham ◽  
Julia M. Davies ◽  
...  
Keyword(s):  
Ion Channel ◽  
Cyclic Nucleotide ◽  
Plant Immunity ◽  
Extracellular Atp ◽  
Atp Signaling

Functional expression of purinergic P2X7 receptors in pregnant rat myometrium

2010 ◽  
Vol 298 (4) ◽  
pp. R1117-R1124 ◽  
Author(s):  
Hiroshi Miyoshi ◽  
Kaoru Yamaoka ◽  
Satoshi Urabe ◽  
Miho Kodama ◽  
Yoshiki Kudo
Keyword(s):  
P2x7 Receptor ◽  
Uterine Contraction ◽  
Extracellular Atp ◽  
Receptor Expression ◽  
P2x Receptor ◽  
Receptor Subtype ◽  
P2x7 Receptors ◽  
Pregnant Rat ◽  
Myometrial Cells ◽  
Induced Currents

ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractility. Purinergic P2 receptor expression has been reported in the myometrium, using molecular biology, but the functional identity of the receptor subtype has not been determined. In this study, ATP-induced currents were recorded and characterized in single myometrial cells from pregnant rats using whole cell patch clamping. Extracellular ATP was applied in the range of 10 μM-1 mM and induced currents with an EC50 of 74 μM, with no desensitization, time dependency, or voltage dependency. The currents induced carried multiple monovalent cations, with conductances ranked as K+ > Cs+ > Li+ > Na+. They were activated by P2X receptor agonists, with their effectiveness ranked as 2′,3′- O-(4-benzoylbenzoyl)-ATP >> ATP > αβ-methylene-ATP > 2-methylthio ATP ≥ UTP ≥ GTP > ADP. These currents were blocked by the selective P2X7 receptor antagonist 3-[5-(2,3-dichlorophenyl)-1 H-tetrazol-1-yl]methyl pyridine (A-438079). We therefore concluded that ATP-induced currents in rat myometrial cells crossed cell membranes via P2X7 receptors. We further showed that the ATP-induced currents were blocked by extracellular Mg2+ (IC50 = 0.26 mM). Clinically, administering extracellular Mg2+ is known to inhibit uterine contraction. It therefore seems likely that uterine contraction may be induced by raised extracellular ATP and suppressed via Mg2+ inhibiting P2X7 receptors. Further research is needed into the P2X7 receptor as a therapeutic target in abnormal uterine contraction, as a possible treatment for premature labor.

The Cytolytic P2Z Receptor for Extracellular ATP Identified as a P2X Receptor (P2X7)

Science ◽  
1996 ◽  
Vol 272 (5262) ◽  
pp. 735-738 ◽  
Author(s):  
A. Surprenant ◽  
F. Rassendren ◽  
E. Kawashima ◽  
R. A. North ◽  
G. Buell
Keyword(s):  
Extracellular Atp ◽  
P2x Receptor

scholarly journals P2X Receptors: Potential Therapeutic Targets for Symptoms Associated With Lung Cancer — A Mini Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Yonglin Mai ◽  
Zhihua Guo ◽  
Weiqiang Yin ◽  
Nanshan Zhong ◽  
Peter V. Dicpinigaitis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Purinergic Signaling ◽  
Cell Metabolism ◽  
Tumor Development ◽  
P2x Receptors ◽  
Extracellular Atp ◽  
Symptom Clusters ◽  
P2x Receptor ◽  
Therapeutic Interventions ◽  
Receptor Antagonists

Symptoms associated with lung cancer mainly consist of cancer-associated pain, cough, fatigue, and dyspnea. However, underlying mechanisms of lung cancer symptom clusters remain unclear. There remains a paucity of effective treatment to ameliorate debilitating symptoms and improve the quality of life of lung cancer survivors. Recently, extracellular ATP and its receptors have attracted increasing attention among researchers in the field of oncology. Extracellular ATP in the tumor microenvironment is associated with tumor cell metabolism, proliferation, and metastasis by driving inflammation and neurotransmission via P2 purinergic signaling. Accordingly, ATP gated P2X receptors expressed on tumor cells, immune cells, and neurons play a vital role in modulating tumor development, invasion, progression, and related symptoms. P2 purinergic signaling is involved in the development of different lung cancer-related symptoms. In this review, we summarize recent findings to illustrate the role of P2X receptors in tumor proliferation, progression, metastasis, and lung cancer- related symptoms, providing an outline of potential anti-neoplastic activity of P2X receptor antagonists. Furthermore, compared with opioids, P2X receptor antagonists appear to be innovative therapeutic interventions for managing cancer symptom clusters with fewer side effects.

scholarly journals P2X-GCaMPs as versatile tools for imaging extracellular ATP signaling

2020 ◽  
Author(s):  
Matthias Ollivier ◽  
Juline Beudez ◽  
Nathalie Linck ◽  
Thomas Grutter ◽  
Vincent Compan ◽  
...  
Keyword(s):  
Signal To Noise Ratio ◽  
Atp Release ◽  
Cell Types ◽  
Extracellular Atp ◽  
P2x Receptor ◽  
High Signal ◽  
Calcium Sensors ◽  
Extracellular Signaling

AbstractAdenosine 5’ triphosphate (ATP) is an extracellular signaling molecule involved in numerous physiological and pathological processes. Yet, in situ characterization of the spatiotemporal dynamic of extracellular ATP is still challenging due to the lack of sensor with appropriate specificity, sensitivity and kinetics. Here we report the development of biosensors based on the fusion of cation permeable ATP receptors (P2X) to genetically encoded calcium sensors (GECI). By combining the features of P2X receptors with the high signal to noise ratio of GECIs, we generated ultrasensitive green and red fluorescent sniffers that detect nanomolar ATP concentrations in situ and also enable the tracking of P2X receptor activity. We provide the proof of concept that these sensors can dynamically track ATP release evoked by neuronal depolarization or by extracellular hypotonicity. Targeting these P2X-based biosensors to diverse cell types should advance our knowledge of extracellular ATP dynamics in vivo.

scholarly journals Single-walled Carbon Nanotubes Are a New Class of Ion Channel Blockers

2003 ◽  
Vol 278 (50) ◽  
pp. 50212-50216 ◽  
Author(s):  
Ki Ho Park ◽  
Manish Chhowalla ◽  
Zafar Iqbal ◽  
Federico Sesti
Keyword(s):  
Carbon Nanotubes ◽  
Ion Channel ◽  
Single Walled Carbon Nanotubes ◽  
Channel Blockers ◽  
Single Walled Carbon ◽  
Ion Channel Blockers ◽  
New Class ◽  
Walled Carbon Nanotubes
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