Pathophysiological roles of extracellular nucleotides in glial cells: differential expression of purinergic receptors in resting and activated microglia

Bianco, Fabio; Fumagalli, Marta; Pravettoni, Elena; D’Ambrosi, Nadia; Volonté, Cinzia; Matteoli, Michela; Abbracchio, Maria P.; Verderio, Claudia

doi:10.1016/j.brainresrev.2004.12.004

Cited by 141 publications

(124 citation statements)

References 48 publications

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“…Although the expression of P2Y 4 receptors in microglia is well documented, e.g. (Bianco et al, 2005;Fumagalli et al, 2003), the lack of specific tools to probe the receptor mean that a full understanding of its role remains elusive. In addition to P2Y 2 and P2Y 4 , P2Y 6 receptors are also activated by uridine nucleotides, particularly UDP.…”

Section: The Role Of P2y Receptors In Neuroinflammationmentioning

confidence: 99%

“…P2Y 13 receptors expressed by cerebellar astrocytes and neurons confer neuroprotection through the activation of the GSK3 ERK1/2 pathway (Perez-Sen et al, 2015). Finally P2Y 14 receptors are also expressed by microglia, however these receptors are exclusively sensitive to UDP-glucose and other conjugates of UDP but not adenine or uracil nucleotides (Bianco et al, 2005). Again, the participation of P2Y 14 receptors in neuroinflammation may be identified by future studies, as their role in the regulation of cell stress and repair in the periphery implicate a similar role in the nervous system (Jacobson et al, 2015).…”

Section: The Role Of P2y Receptors In Neuroinflammationmentioning

confidence: 99%

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Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

et al. 2016

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a b s t r a c tThe principle functions of neuroinflammation are to limit tissue damage and promote tissue repair in response to pathogens or injury. While neuroinflammation has utility, pathophysiological inflammatory responses, to some extent, underlie almost all neuropathology. Understanding the mechanisms that control the three stages of inflammation (initiation, propagation and resolution) is therefore of critical importance for developing treatments for diseases of the central nervous system. The purinergic signaling system, involving adenosine, ATP and other purines, plus a host of P1 and P2 receptor subtypes, controls inflammatory responses in complex ways. Activation of the inflammasome, leading to release of pro-inflammatory cytokines, activation and migration of microglia and altered astroglial function are key regulators of the neuroinflammatory response. Here, we review the role of P1 and P2 receptors in mediating these processes and examine their contribution to disorders of the nervous system. Firstly, we give an overview of the concept of neuroinflammation. We then discuss the contribution of P2X, P2Y and P1 receptors to the underlying processes, including a discussion of cross-talk between these different pathways. Finally, we give an overview of the current understanding of purinergic contributions to neuroinflammation in the context of specific disorders of the central nervous system, with special emphasis on neuropsychiatric disorders, characterized by chronic low grade inflammation or maternal inflammation. An understanding of the important purinergic contribution to neuroinflammation underlying neuropathology is likely to be a necessary step towards the development of effective interventions.

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Section: The Role Of P2y Receptors In Neuroinflammationmentioning

confidence: 99%

Section: The Role Of P2y Receptors In Neuroinflammationmentioning

confidence: 99%

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

et al. 2016

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“…In our study, NTPDase1 is also expressed by axons of GCs in the nerve fiber layer. In this layer, NTPDase1 might also be expressed by microglia or astrocytes, which have been shown to harbor P2X receptors (Bianco et al, 2005;Xiang and Burnstock, 2005) and to release ATP (Newman, 2006). The regionalized presence of NTPDase1 would suggest a rapid hydrolysis of both ATP and ADP released in the vicinity of the enzyme, limiting the activation of P2 receptors and quickly rising extracellular AMP concentration.…”

Section: Ntpdase1 Localization In the Retina Of Mousementioning

confidence: 99%

Immunocytochemical localization of NTPDases1 and 2 in the neural retina of mouse and zebrafish

Ricatti

Alfie

Lavoie

et al. 2008

Synapse

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Here we show a detailed immunocytochemical localization of two enzymes of the ENTPDase family in the retinal layers of two vertebrate species, namely, the mouse and the zebrafish. In the mouse retina, NTPDase2 was chiefly localized in Mü ller glia and ganglion cell processes. NTPDase1 was located on neurons as well, since it was expressed by horizontal and ganglion cell processes, suggesting that nucleotides such as ATP and ADP can be hydrolyzed at the surface of these cells. NTPDase1 was also detected in intraretinal blood vessels of the mouse. Regarding zebrafish, NTPDases1 and 2 seem to be differentially localized in horizontal cell processes, photoreceptor segments, and ganglion cell dendrites and axons, but absent from Mü ller glia. Moreover, NTPDases1 and 2 appear to be expressed within the germinal margin of the zebrafish retina that contains proliferative and differentiating cells. Retinal homogenates from both species exhibited ecto-ATPase activity which might be attributed at least to NTPDases1 and 2, whose expression is described in this report. Our results suggest a compartmentalized regulation of extracellular nucleotide/nucleoside concentration in the retinal layers, supporting a relevant role for extracellular nucleotide mediated-signaling in vertebrate retinas. Synapse 63:291-307,

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“…It has been reported recently that P2X 7 receptors are expressed in central and spinal cord neurons [19][20][21][22]. Brain glial cells (microglia, astrocytes, and Muller cells), bone cells (osteoblasts, osteoclasts, and osteocytes), and epithelial and endothelial cells are also rich in P2X 7 receptors [23][24][25][26][27][28][29]. Expression of P2X 7 receptors has also been demonstrated in the enteric nervous system of the small intestine, kidney, urinary tract, uterus, and liver [30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of a novel variant of the human P2X7 receptor resulting in gain of function

Sun

Chu

Singh

et al. 2009

Purinergic Signalling

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The P2X 7 receptor exhibits significant allelic polymorphism in humans, with both loss and gain of function variants potentially impacting on a variety of infectious and inflammatory disorders. At least five loss-offunction polymorphisms (G150R, R307Q, T357S, E496A, and I568N) and two gain-of-function polymorphisms (H155Y and Q460R) have been identified and characterized to date. In this study, we used RT-PCR cloning to isolate and characterize P2X 7 cDNA clones from human PBMCs and THP-1 cells. A previously unreported variant with substitutions of V80M and A166G was identified. When expressed in HEK293 cells, this variant exhibited heightened sensitivity to the P2X 7 agonist (BzATP) relative to the most frequent allele, as shown by pore formation measured by fluorescent dye uptake into cells. Mutational analyses showed that A166G alteration was critical for the gain-offunction change, while V80M was not. Full-length variants with multiple previously identified nonsynonymous SNPs (H155Y, H270R, A348T, and E496A) were also identified. Distinct functional phenotypes of the P2X 7 variants or mutants constructed with multiple polymorphisms were observed. Gain-of-function variations (A166G or H155Y) could not rescue the loss-of-function E496A polymorphism. Synergistic effects of the gain-of-function variations were also observed. We also identified the A348T alteration as a weak gain-of-function variant. Thus, these results identify the new gain-of-function variant A166G and demonstrate that multiple-gene polymorphisms contribute to functional phenotypes of the human P2X 7 receptor.Furthermore, the results demonstrate that the C-terminal of the cysteine-rich domain 1 of P2X 7 is critical for regulation of P2X 7 -mediated pore formation.

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Pathophysiological roles of extracellular nucleotides in glial cells: differential expression of purinergic receptors in resting and activated microglia

Cited by 141 publications

References 48 publications

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

Immunocytochemical localization of NTPDases1 and 2 in the neural retina of mouse and zebrafish

Identification and characterization of a novel variant of the human P2X7 receptor resulting in gain of function

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