Neuronal P2X7 Receptor: Involvement in Neuronal Physiology and Pathology

Miras‐Portugal, M. Teresa; Sebastián-Serrano, Álvaro; García, Laura Pérez; Dı́az-Hernández, Miguel

doi:10.1523/jneurosci.3104-16.2017

Cited by 114 publications

(106 citation statements)

References 95 publications

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“…et al, 2017). The P2X7R is widely expressed in diverse tissues, including hematopoietic cells (Feng et al, 2016), neurons (Miras-Portugal et al, 2017), glia (Stokes et al, 2015;Kaczmarek-Hajek et al, 2018), bone (Agrawal and Gartland, 2015), muscle (Fabbrizio et al, 2019), endothelium (Green et al, 2018), epithelium (Woods et al, 2012), and immune cells (Ferrari et al, 1997). In the exocrine pancreas, P2X7Rs have been shown to be primarily expressed in pancreatic ductal cells where they may contribute to secretory regulation through induction of cation fluxes and interaction with cholinergic signaling (Novak et al, 2010;Burnstock and Novak, 2012).…”

Section: The Role Of P2 Receptors In Salivary Gland Functionmentioning

confidence: 99%

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

et al. 2020

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Although often overlooked in our daily lives, saliva performs a host of necessary physiological functions, including lubricating and protecting the oral cavity, facilitating taste sensation and digestion and maintaining tooth enamel. Therefore, salivary gland dysfunction and hyposalivation, often resulting from pathogenesis of the autoimmune disease Sjögren's syndrome or from radiotherapy of the head and neck region during cancer treatment, severely reduce the quality of life of afflicted patients and can lead to dental caries, periodontitis, digestive disorders, loss of taste and difficulty speaking. Since their initial discovery in the 1970s, P2 purinergic receptors for extracellular nucleotides, including ATP-gated ion channel P2X and G protein-coupled P2Y receptors, have been shown to mediate physiological processes in numerous tissues, including the salivary glands where P2 receptors represent a link between canonical and non-canonical saliva secretion. Additionally, extracellular nucleotides released during periods of cellular stress and inflammation act as a tissue alarmin to coordinate immunological and tissue repair responses through P2 receptor activation. Accordingly, P2 receptors have gained widespread clinical interest with agonists and antagonists either currently undergoing clinical trials or already approved for human use. Here, we review the contributions of P2 receptors to salivary gland function and describe their role in salivary gland dysfunction. We further consider their potential as therapeutic targets to promote physiological saliva flow, prevent salivary gland inflammation and enhance tissue regeneration.

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Section: The Role Of P2 Receptors In Salivary Gland Functionmentioning

confidence: 99%

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

et al. 2020

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“…P2X7 is also expressed in central nervous system cells: microglia, astrocytes and oligodendrocytes, whereas its presence in neurons is still a subject of the debate (Illes et al, 2017;Miras-Portugal et al, 2017;Kaczmarek-Hajek et al, 2018). Importantly, glia and neurons use the extracellular ATP to communicate and to maintain the homeostasis in the brain; moreover, ATP may be also released from damaged CNS cells (Rivera et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

P2X7 receptor activity landscape in rat and human glioma cell lines

2020

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P2X7 is a commonly expressed purinergic receptor, which functions as a cation-permeable channel in the plasma membrane. In certain circumstances, the receptor may also form a large transmembrane pore what results in cell death. P2X7 receptors control numerous physiological and pathological cellular processes and their overexpression is often associated with cancer progression. As nucleotides are important signaling molecules in the central nervous system, P2X7 plays also an important but ambiguous role in glioma biology with contrary observations originating from different glioma models. Therefore, the aim of our research was to investigate P2X7 receptor expression and functions in three human (U-87 MG, U-138 MG, U-251 MG) and one rat (C6) glioma cell lines. Although the receptor mRNA and protein were present in all the studied cells, we found profound differences in their level. We also encountered a problem with one human cell lines authenticity (U-87 MG) and excluded it from most of the experiments. Interestingly, there was no clear dependency between P2X7 receptor level, calcium signal and pore formation ability in the studied glioma lines. In U-138 human cell line, the receptor seemed to be inactive, while in U-251 human and C6 rat cell line its activation resulted in calcium influx and large pore formation. However, the viability of studied cells upon the administration of specific P2X7 agonist -BzATP -was not affected for U-138 and U-251, whereas for C6 cells a stimulatory effect was observed. Our results stress the variability of P2X7 signaling in glioma models and the need for future research which would take into account the complicated landscape of the receptor signaling in the brain.

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“…Furthermore, it is still unclear in which kinds of cells P2 × 7R is expressed. P2 × 7R was hardly found in neurons [42] and was majorly found in glial cells [43]. It is essential to clear it out in ZDF rats.…”

Section: Introductionmentioning

confidence: 96%

Transcutaneous auricular vagal nerve stimulation inhibits P2X7R expression in limbic brain regions and reverses depression-like behavior in Zucker diabetic fatty rats

Wang

et al. 2020

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Background Previous studies confirmed that Zucker diabetic fatty rats (ZDF, fa/fa) develop type 2 diabetes (T2D) with depression-like behavior innately, and transcutaneous auricular vagal nerve stimulation (taVNS) was found to have anti-diabetic and anti-depressive effect in ZDF rats. However, there is still a lack of molecular-biological evidence that ZDF rats are a good rodent model of depression, and how does taVNS take the anti-depressive effect to the ZDF rats. P2 × 7R, a purinergic receptor most-related to inflammation and depression, is found to be elevated in depressed brains and is gradually considered as a potential therapeutic target for depression. Methods We deployed taVNS and transcutaneous none vagal nerve stimulation (tnVNS) to ZDF rats. We applied forced swimming test (FST) to evaluate to the depression-like behavior of the rats. We used Western blot to test the P2 × 7R expression in the hypothalamus, amygdala, hippocampus, prefrontal cortex, and cingulate cortex of the rats. Furthermore, we used immunohistochemical staining to colocalize the P2 × 7R expressing cells in the ZDF rats’ brains. Results We found that compared with their lean littermates (ZL rats), naïve ZDF rats developed depression-like behavior innately with elevated P2 × 7R expression in their limbic brain regions (hypothalamus, amygdala, hippocampus, prefrontal cortex, and cingulate cortex); and taVNS but not tnVNS inhibited the P2 × 7R expression in their limbic brain regions and reversed the depression-like behavior. Moreover, P2 × 7R was found majorly expressing in astrocytes and microglia of ZDF rats. Conclusions ZDF rats are a good rodent model of depression, and taVNS plays an anti-depressive effect in ZDF rats by inhibiting glial P2 × 7R expression in their limbic brain regions.

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Neuronal P2X7 Receptor: Involvement in Neuronal Physiology and Pathology

Cited by 114 publications

References 95 publications

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

P2X7 receptor activity landscape in rat and human glioma cell lines

Transcutaneous auricular vagal nerve stimulation inhibits P2X7R expression in limbic brain regions and reverses depression-like behavior in Zucker diabetic fatty rats

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