scholarly journals Cross talk between P2 purinergic receptors modulates extracellular ATP-mediated interleukin-10 production in rat microglial cells

2008 ◽  
Vol 40 (1) ◽  
pp. 19 ◽  
Author(s):  
Dong Reoyl Seo ◽  
Soo Yoon Kim ◽  
Kyung You Kim ◽  
Hwan Goo Lee ◽  
Ju Hyun Moon ◽  
...  
Keyword(s):  
Cross Talk ◽  
Purinergic Receptors ◽  
Interleukin 10 ◽  
Extracellular Atp ◽  
Microglial Cells ◽  
P2 Purinergic Receptors

P2X7 receptor cross-talk regulates ATP-induced pannexin 1 internalization

2017 ◽  
Vol 474 (13) ◽  
pp. 2133-2144 ◽  
Author(s):  
Andrew K.J. Boyce ◽  
Leigh Anne Swayne
Keyword(s):  
Nervous System ◽  
Cross Talk ◽  
Purinergic Receptors ◽  
Atp Release ◽  
Extracellular Atp ◽  
Signalling Pathways ◽  
Physical Interaction ◽  
Cell Periphery ◽  
Dependent Manner ◽  
Pannexin 1

In the nervous system, extracellular ATP levels transiently increase in physiological and pathophysiological circumstances, effecting key signalling pathways in plasticity and inflammation through purinergic receptors. Pannexin 1 (Panx1) forms ion- and metabolite-permeable channels that mediate ATP release and are particularly enriched in the nervous system. Our recent study demonstrated that elevation of extracellular ATP triggers Panx1 internalization in a concentration- and time-dependent manner. Notably, this effect was sensitive to inhibition of ionotropic P2X7 purinergic receptors (P2X7Rs). Here, we report our novel findings from the detailed investigation of the mechanism underlying P2X7R–Panx1 cross-talk in ATP-stimulated internalization. We demonstrate that extracellular ATP triggers and is required for the clustering of P2X7Rs and Panx1 on Neuro2a cells through an extracellular physical interaction with the Panx1 first extracellular loop (EL1). Importantly, disruption of P2X7R–Panx1 clustering by mutation of tryptophan 74 within the Panx1 EL1 inhibits Panx1 internalization. Notably, P2X7R–Panx1 clustering and internalization are independent of P2X7R-associated intracellular signalling pathways (Ca2+ influx and Src activation). Further analysis revealed that cholesterol is required for ATP-stimulated P2X7R–Panx1 clustering at the cell periphery. Taken together, our data suggest that extracellular ATP induces and is required for Panx1 EL1-mediated, cholesterol-dependent P2X7R–Panx1 clustering and endocytosis. These findings have important implications for understanding the role of Panx1 in the nervous system and provide important new insights into Panx1–P2X7R cross-talk.

scholarly journals Purinergic signaling, DAMPs, and inflammation

2020 ◽  
Vol 318 (5) ◽  
pp. C832-C835 ◽  
Author(s):  
Francesco Di Virgilio ◽  
Alba Clara Sarti ◽  
Robson Coutinho-Silva
Keyword(s):  
Plasma Membrane ◽  
Purinergic Receptors ◽  
Purinergic Signaling ◽  
Extracellular Atp ◽  
Main Metabolite ◽  
P2 Purinergic Receptors ◽  
Evolutionary Features ◽  
Multicellular Organisms ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Danger sensing is one of the most fundamental evolutionary features enabling multicellular organisms to perceive potential threats, escape from risky situations, fight actual intruders, and repair damage. Several endogenous molecules are used to “signal damage,” currently referred to as “alarmins” or “damage-associated molecular patterns” (DAMPs), most being already present within all cells (preformed DAMPs), and thus ready to be released, and others neosynthesized following injury. Over recent years it has become overwhelmingly clear that adenosine 5′-triphosphate (ATP) is a ubiquitous and extremely efficient DAMP (thus promoting inflammation), and its main metabolite, adenosine, is a strong immunosuppressant (thus dampening inflammation). Extracellular ATP ligates and activates the P2 purinergic receptors (P2Rs) and is then degraded by soluble and plasma membrane ecto-nucleotidases to generate adenosine acting at P1 purinergic receptors (P1Rs). Extracellular ATP, P2Rs, ecto-nucleotidases, adenosine, and P1Rs are basic elements of the purinergic signaling network and fundamental pillars of inflammation.

Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides

1993 ◽  
Vol 265 (3) ◽  
pp. C577-C606 ◽  
Author(s):  
G. R. Dubyak ◽  
C. el-Moatassim
Keyword(s):  
Purinergic Receptors ◽  
Plasma Membranes ◽  
Surface Membrane ◽  
Cell Types ◽  
Extracellular Atp ◽  
Secretory Cells ◽  
Atp Receptors ◽  
Immune Effector ◽  
Functional Changes ◽  
P2 Purinergic Receptors

Extracellular ATP, at micromolar concentrations, induces significant functional changes in a wide variety of cells and tissues. ATP can be released from the cytosol of damaged cells or from exocytotic vesicles and/or granules contained in many types of secretory cells. There are also efficient extracellular mechanisms for the rapid metabolism of released nucleotides by ecto-ATPases and 5'-nucleotidases. The diverse biological responses to ATP are mediated by a variety of cell surface receptors that are activated when ATP or other nucleotides are bound. The functionally identified nucleotide or P2-purinergic receptors include 1) ATP receptors that stimulate G protein-coupled effector enzymes and signaling cascades, including inositol phospholipid hydrolysis and the mobilization of intracellular Ca2+ stores; 2) ATP receptors that directly activate ligand-gated cation channels in the plasma membranes of many excitable cell types; 3) ATP receptors that, via the rapid induction of surface membrane channels and/or pores permeable to ions and endogenous metabolites, produce cytotoxic or activation responses in macrophages and other immune effector cells; and 4) ADP receptors that trigger rapid ion fluxes and aggregation responses in platelets. Current research in this area is directed toward the identification and structural characterization of these receptors by biochemical and molecular biological approaches.

scholarly journals Role of P2-purinergic receptors in rat Leydig cell steroidogenesis

1996 ◽  
Vol 320 (2) ◽  
pp. 499-504 ◽  
Author(s):  
Carlo FORESTA ◽  
Marco ROSSATO ◽  
Andrea NOGARA ◽  
Francesco GOTTARDELLO ◽  
Paola BORDON ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Purinergic Receptors ◽  
External Medium ◽  
Purinergic Receptor ◽  
Extracellular Atp ◽  
Receptor Subtype ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Testosterone Secretion ◽  
P2 Purinergic Receptors

The present study investigated the effects of extracellular ATP on the intracellular calcium ion concentration ([Ca2+]i) and testosterone production in isolated adult rat Leydig cells. This nucleotide caused an increase in [Ca2+]i, with a maximal effect at a concentration of 100 µM ATP, comprising a rapid initial spike followed by a long-lasting plateau. The first rapid spike was dependent on the release of Ca2+ from internal stores, since it also occurred in Ca2+-free medium and was abolished after depletion of internal stores with thapsigargin. The second, long-lasting, phase was dependent on the influx of Ca2+ from the extracellular medium. After 3 h of incubation, extracellular ATP stimulated testosterone secretion in a dose-dependent manner, with a maximal effect at 100 µM. Activation of steroidogenesis by ATP was fully dependent on the presence of Ca2+ in the external medium. Among different nucleotides, only ATP, adenosine 5´-[γ-thio]triphosphate, UTP, benzoylbenzoic-ATP and 2-methylthio-ATP were effective in inducing both the rise in [Ca2+]i and testosterone secretion. These effects were blocked by preincubation of Leydig cells with oxidized ATP, an inhibitor of the P2Z-purinergic receptor subtype. These results show that rat Leydig cells possess P2-purinergic receptors whose activation triggers an increase in [Ca2+]i due to the release of Ca2+ from internal stores and Ca2+ influx from the external medium. The stimulatory effect of extracellular ATP on testosterone secretion seems to be coupled to the influx of Ca2+ from the external medium.

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