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Purinergic Signalling

Geoffrey Burnstock
No abstract text is available yet for this article.
December 5, 2018: Purinergic Signalling
Sílvia Oliveira, Ana Paula Ardais, Clarissa Ribeiro Bastos, Marta Gazal, Karen Jansen, Luciano de Mattos Souza, Ricardo Azevedo da Silva, Manuella Pinto Kaster, Diogo Rizzato Lara, Gabriele Ghisleni
Genetic variants involved in adenosine metabolism and its receptors were associated with increased risk for psychiatric disorders, including anxiety, depression, and schizophrenia. Here, we examined an association between a single nucleotide polymorphism in A2A receptor gene (ADORA2A, rs2298383 SNP) with current depressive episode and symptom profile. A total of 1253 individuals from a cross-sectional population-based study were analyzed by the Mini International Neuropsychiatric Interview 5.0. Our data showed that the TT genotype of ADORA2A rs2298383 SNP was associated with reduced risk for depression when compared to the CC/CT genotypes (p = 0...
December 3, 2018: Purinergic Signalling
M Cieślak, K Roszek, M Wujak
Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disorder characterized by degeneration of upper motor neurons in the brainstem and lower motor neurons in the spinal cord. Multiple mechanisms of motor neuron injury have been implicated, including more than 20 different genetic factors. The pathogenesis of ALS consists of two stages: an early neuroprotective stage and a later neurotoxic. During early phases of disease progression, the immune system through glial and T cell activities provides anti-inflammatory factors that sustain motor neuron viability...
November 14, 2018: Purinergic Signalling
Oleg Palygin, Daria V Ilatovskaya, Vladislav Levchenko, Christine A Klemens, Lashodya Dissanayake, Anna Marie Williams, Tengis S Pavlov, Alexander Staruschenko
Polycystic kidney diseases (PKDs) are a group of inherited nephropathies marked by formation of fluid-filled cysts along the nephron. Growing evidence suggests that in the kidney formation of cysts and alteration of cystic electrolyte transport are associated with purinergic signaling. PCK/CrljCrl-Pkhd1pck/CRL (PCK) rat, an established model of autosomal recessive polycystic kidney disease (ARPKD), was used here to test this hypothesis. Cystic fluid of PCK rats and their cortical tissues exhibited significantly higher levels of ATP compared to Sprague Dawley rat kidney cortical interstitium as assessed by highly sensitive ATP enzymatic biosensors...
November 11, 2018: Purinergic Signalling
Fabian Doktor, Philipp Prager, Peter Wiedemann, Leon Kohen, Andreas Bringmann, Margrit Hollborn
Retinal hypoxia is a major condition of the chronic inflammatory disease age-related macular degeneration. Extracellular ATP is a danger signal which is known to activate the NLRP3 inflammasome in various cell systems. We investigated in cultured human retinal pigment epithelial (RPE) cells whether hypoxia alters the expression of inflammasome-associated genes and whether purinergic receptor signaling contributes to the hypoxic expression of key inflammatory (NLRP3) and angiogenic factor (VEGF) genes. Hypoxia and chemical hypoxia were induced by a 0...
November 10, 2018: Purinergic Signalling
Wei Zhang, Shumin Zhou, Guoping Liu, Fanqiang Kong, Song Chen, Hua Yan
Physiologically, retinal pigment epithelium (RPE) expresses high levels of CD73 in their membrane, converting AMP to immune suppressive adenosine, mediates an anti-inflammatory effect. However, after being exposed to inflammatory factors, RPE rapidly becomes CD73-negative cells, which render RPE's immune suppressive function and accelerate local inflammation. Here, we investigated the mechanism leading to the loss of membrane CD73 in RPE. We found the controversy that when membrane CD73 was significantly diminished in inflammatory RPE, Cd73 mRNA levels were not changed at all...
November 3, 2018: Purinergic Signalling
Li Wang, Xiaoqian Feng, Bing Hu, Qingqing Xia, Xiuqin Ni, Yinli Song
The P2X4 receptor (P2X4R) contributes to airway inflammation and airway remodeling in mice with allergic asthma. However, the molecular mechanism by which P2X4R affects the airway remodeling in allergic asthma remains largely unknown. We established an allergic asthma model by ovalbumin (OVA) inhalation in BALB/c mice. Compared with the mice in the control group, the expression of proliferating cell nuclear antigen (PCNA) increased and that of alpha-smooth muscle actin (α-SMA) decreased in the OVA-challenged mice...
November 1, 2018: Purinergic Signalling
Lars Petter Jordheim
Purine metabolism is depending on a large amount of enzymes to ensure cellular homeostasis. Among these enzymes, we have been interested in the 5'-nucleotidase cN-II and its role in cancer biology and in response of cancer cells to treatments. This protein has been cited and studied in a large number of papers published during the last decade for its involvement in non-cancerous pathologies such as hereditary spastic paraplegia, schizophrenia, and blood pressure regulation. Here, we review these articles in order to give an overview of the recently discovered clinical relevance of cN-II...
October 25, 2018: Purinergic Signalling
Anna S Miteva, Alexander E Gaydukov, Valery I Shestopalov, Olga P Balezina
P2X7 receptors are present in presynaptic membranes of motor synapses, but their regulatory role in modulation of neurotransmitter release remains poorly understood. P2X7 receptors may interact with pannexin 1 channels to form a purinergic signaling unit. The potential mechanism of P2X7 receptor-dependent modulation of acetylcholine (ACh) release was investigated by recording miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) in neuromuscular junctions of wild-type (WT) and pannexin 1 knockout (Panx1-/- ) mice...
October 25, 2018: Purinergic Signalling
Marek Cieślak, Andrzej Wojtczak
Etiology of the Alzheimer's disease (AD) is not fully understood. Different pathological processes are considered, such as amyloid deposition, tau protein phosphorylation, oxidative stress (OS), metal ion disregulation, or chronic neuroinflammation. Purinergic signaling is involved in all these processes, suggesting the importance of nucleotide receptors (P2X and P2Y) and adenosine receptors (A1, A2A, A2B, A3) present on the CNS cells. Ecto-purines, ecto-pyrimidines, and enzymes participating in their metabolism are present in the inter-cellular spaces...
October 25, 2018: Purinergic Signalling
Anna Bin, Valentina Caputi, Michela Bistoletti, Monica Montopoli, Rocchina Colucci, Luca Antonioli, Sara De Martin, Ignazio Castagliuolo, Genny Orso, Cristina Giaroni, Patrizia Debetto, Maria Cecilia Giron
Adenosine is a versatile signaling molecule recognized to physiologically influence gut motor functions. Both the duration and magnitude of adenosine signaling in enteric neuromuscular function depend on its availability, which is regulated by the ecto-enzymes ecto-5'-nucleotidase (CD73), alkaline phosphatase (AP), and ecto-adenosine deaminase (ADA) and by dipyridamole-sensitive equilibrative transporters (ENTs). Our purpose was to assess the involvement of CD73, APs, ecto-ADA in the formation of AMP-derived adenosine in primary cultures of ileal myofibroblasts (IMFs)...
September 29, 2018: Purinergic Signalling
Stephanie Kuhn, Katrin Splith, Cindy Ballschuh, Linda Feldbrügge, Felix Krenzien, Georgi Atanasov, Christian Benzing, Hans-Michael Hau, Cornelius Engelmann, Thomas Berg, Jan Schulte Am Esch, Johann Pratschke, Simon C Robson, Moritz Schmelzle
Plasma microparticles (MP) bear functional active ectonucleotidases of the CD39 family with implications in vascular inflammation. MP appear to be able to fuse with cells and transfer genetic information. Here, we tested whether levels of different immunomodulatory microRNAs (miRs) in plasma MP are modulated by CD39 after experimental hepatectomy. We further investigated whether horizontal transfer of miR-142-3p between mononuclear (MNC) and endothelial cells via MP is regulated by purinergic signaling. Partial hepatectomy was performed in C57BL/6 wild type and Cd39 null mice...
September 22, 2018: Purinergic Signalling
Jesús Pintor
The recent discovery of the photoreceptor melanopsin in lens epithelial cells has opened the possibility of modulating this protein by light stimulation. Experiments carried out on New Zealand white rabbits have demonstrated that the release of ATP from the lens to the aqueous humor can be reduced either when a yellow filter or a melanopsin antagonist is used. Compared to control (1.10 ± 0.15 μM ATP), the application of a yellow filter (λ465-480) reduced ATP in the aqueous humor 70%, while the melanopsin antagonist AA92593 reduced the presence of ATP 63% (n = 5), an effect which was also obtained with the PLC inhibitor U73122...
September 20, 2018: Purinergic Signalling
Tali Fishman Jacob, Vijay Singh, Mudit Dixit, Tamar Ginsburg-Shmuel, Begoña Fonseca, Jesus Pintor, Moussa B H Youdim, Dan T Major, Orly Weinreb, Bilha Fischer
Extracellular nucleotides can regulate the production/drainage of the aqueous humor via activation of P2 receptors, thus affecting the intraocular pressure (IOP). We evaluated 5-OMe-UDP(α-B), 1A, a potent P2Y6-receptor agonist, for reducing IOP and treating glaucoma. Cell viability in the presence of 1A was measured using [3-(4, 5-dimethyl-thiazol-2-yl) 2, 5-diphenyl-tetrazolium bromide] (MTT) assay in rabbit NPE ciliary non-pigmented and corneal epithelial cells, human retinoblastoma, and liver Huh7 cells...
September 2018: Purinergic Signalling
Ruihua Ji, Jiao Zhu, Dan Wang, Qian-Qian Sui, Gillian E Knight, Geoffrey Burnstock, Hongbin Yuan, Zhenghua Xiang
With immunohistochemical and Western blot techniques, P2X1 receptors were detected in the whole mouse gastrointestinal tract and pancreatic islets of mouse and human. (1) δ Cells containing somatostatin (SOM) in the stomach corpus, small intestines, distal colon, pancreatic islets of both mouse and human express P2X1 receptors; (2) strong immunofluorescence of P2X1 receptors was detected in smooth muscle fibers and capillary networks of the villus core of mouse intestine; and (3) P2X1 receptor-immunoreactive neurons were also detected widely in both mouse myenteric and submucosal plexuses, all of which express SOM...
September 2018: Purinergic Signalling
María J Pérez de Lara, Ana Guzmán-Aranguez, Rosa Gómez-Villafuertes, Javier Gualix, María Teresa Miras-Portugal, Jesús Pintor
The pathogenesis of glaucoma involves numerous intracellular mechanisms including the purinergic system contribution. Furthermore, the presence and release of nucleotides and dinucleotides during the glaucomatous damage and the maintenance of degradation machinery through ecto-nucleotidase activity are participating in the modulation of the suitable extracellular complex balance. The aim of this study was to investigate the levels of diadenosine tetraphosphate (Ap4 A) and the pattern of ecto-nucleotidase activity expression in glaucomatous retinas during the progress the pathology...
September 2018: Purinergic Signalling
Hitoshi Tanigawa, Futoshi Toyoda, Kosuke Kumagai, Noriaki Okumura, Tsutomu Maeda, Hiroshi Matsuura, Shinji Imai
Extracellular ATP regulates various cellular functions by engaging multiple subtypes of P2 purinergic receptors. In many cell types, the ionotropic P2X7 receptor mediates pathological events such as inflammation and cell death. However, the importance of this receptor in chondrocytes remains largely unexplored. Here, we report the functional identification of P2X7 receptor in articular chondrocytes and investigate the involvement of P2X7 receptors in ATP-induced cytotoxicity. Chondrocytes were isolated from rabbit articular cartilage, and P2X7 receptor currents were examined using the whole-cell patch-clamp technique...
September 2018: Purinergic Signalling
Daniela F Passos, Viviane M Bernardes, Jean L G da Silva, Maria R C Schetinger, Daniela Bitencourt Rosa Leal
Infection by human immunodeficiency virus (HIV) causes the acquired immune deficiency syndrome (AIDS), which has devastating effects on the host immune system. HIV entry into host cells and subsequent viral replication induce a proinflammatory response, hyperactivating immune cells and leading them to death, disfunction, and exhaustion. Adenosine is an immunomodulatory molecule that suppresses immune cell function to protect tissue integrity. The anti-inflammatory properties of adenosine modulate the chronic inflammation and immune activation caused by HIV...
August 10, 2018: Purinergic Signalling
Tomasz Grygorowicz, Beata Dąbrowska-Bouta, Lidia Strużyńska
Purinergic P2X receptors, when activated under pathological conditions, participate in induction of the inflammatory response and/or cell death. Both neuroinflammation and neurodegeneration represent hallmarks of multiple sclerosis (MS), an autoimmune disease of the central nervous system. In the current study, we examined whether P2X7R is expressed in brain microvasculature of rats subjected to experimental autoimmune encephalomyelitis (EAE) and explore possible relationships with blood-brain barrier (BBB) protein-claudin-5 after administration of P2X7R antagonist-Brilliant Blue G (BBG)...
August 8, 2018: Purinergic Signalling
Seema Ali, Jeremy Turner, Samuel J Fountain
Adipose tissue contains self-renewing multipotent cells termed mesenchymal stromal cells. In situ, these cells serve to expand adipose tissue by adipogenesis, but their multipotency has gained interest for use in tissue regeneration. Little is known regarding the repertoire of receptors expressed by adipose-derived mesenchymal stromal cells (AD-MSCs). The purpose of this study was to undertake a comprehensive analysis of purinergic receptor expression. Mesenchymal stromal cells were isolated from human subcutaneous adipose tissue and confirmed by flow cytometry...
August 7, 2018: Purinergic Signalling
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