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Purinergic Signalling

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https://www.readbyqxmd.com/read/29876714/editor-s-note
#1
EDITORIAL
Geoff Burnstock
No abstract text is available yet for this article.
June 6, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29845461/p2x7-ionotropic-receptor-is-functionally-expressed-in-rabbit-articular-chondrocytes-and-mediates-extracellular-atp-cytotoxicity
#2
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...
May 29, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29770921/neuronal-adenosine-a-2a-receptor-overexpression-is-neuroprotective-towards-3-nitropropionic-acid-induced-striatal-toxicity-a-rat-model-of-huntington-s-disease
#3
Maria Rosaria Domenici, Valentina Chiodi, Mirko Averna, Monica Armida, Antonella Pèzzola, Rita Pepponi, Antonella Ferrante, Michael Bader, Kjell Fuxe, Patrizia Popoli
The A2A adenosine receptor (A2A R) is widely distributed on different cellular types in the brain, where it exerts a broad spectrum of pathophysiological functions, and for which a role in different neurodegenerative diseases has been hypothesized or demonstrated. To investigate the role of neuronal A2A Rs in neurodegeneration, we evaluated in vitro and in vivo the effect of the neurotoxin 3-nitropropionic acid (3-NP) in a transgenic rat strain overexpressing A2A Rs under the control of the neural-specific enolase promoter (NSEA2A rats)...
May 16, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29754194/loss-of-p2x7-receptor-function-dampens-whole-body-energy-expenditure-and-fatty-acid-oxidation
#4
Giacomo Giacovazzo, Savina Apolloni, Roberto Coccurello
The established role of ATP-responsive P2X7 receptor in inflammatory, neurodegenerative, and immune diseases is now expanding to include several aspects of metabolic dysregulation. Indeed, P2X7 receptors are involved in β cell function, insulin secretion, and liability to diabetes, and loss of P2X7 function may increase the risk of hepatic steatosis and disrupt adipogenesis. Recently, body weight gain, abnormal lipid accumulation, adipocyte hyperplasia, increased fat mass, and ectopic fat distribution have been found in P2X7 KO mice...
May 12, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29752619/a-feasibility-study-into-adenosine-triphosphate-measurement-in-exhaled-breath-condensate-a-potential-bedside-method-to-monitor-alveolar-deformation
#5
Philip van der Zee, Peter Somhorst, Jeroen Molinger, Djo Hasan, Diederik Gommers
Recent research suggested an important role for pulmonary extracellular adenosine triphosphate (ATP) in the development of ventilation-induced lung injury. This injury is induced by mechanical deformation of alveolar epithelial cells, which in turn release ATP to the extracellular space. Measuring extracellular ATP in exhaled breath condensate (EBC) may be a non-invasive biomarker for alveolar deformation. Here, we study the feasibility of bedside ATP measurement in EBC. We measured ATP levels in EBC in ten subjects before and after an exercise test, which increases respiratory parameters and alveolar deformation...
May 12, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29752618/tritium-labeled-agonists-as-tools-for-studying-adenosine-a-2b-receptors
#6
Sonja Hinz, Wessam M Alnouri, Ulrich Pleiss, Christa E Müller
A selective agonist radioligand for A2B adenosine receptors (A2B ARs) is currently not available. Such a tool would be useful for labeling the active conformation of the receptors. Therefore, we prepared BAY 60-6583, a potent and functionally selective A2B AR (partial) agonist, in a tritium-labeled form. Despite extensive efforts, however, we have not been able to establish a radioligand binding assay using [3 H]BAY 60-6583. This is probably due to its high non-specific binding and its moderate affinity, which had previously been overestimated based on functional data...
May 11, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29680937/intralesional-uridine-5-triphosphate-utp-treatment-induced-resistance-to-leishmania-amazonensis-infection-by-boosting-th-1-immune-responses-and-reactive-oxygen-species-production
#7
Camila Marques-da-Silva, Mariana M Chaves, Maria Luiza Thorstenberg, Vanessa R Figliuolo, Flávia S Vieira, Suzana P Chaves, José Roberto Meyer-Fernandes, Bartira Rossi-Bergmann, Luiz Eduardo Baggio Savio, Robson Coutinho-Silva
Leishmania amazonensis is the etiologic agent of cutaneous leishmaniasis, an immune-driven disease causing a range of clinical symptoms. Infections caused by L. amazonensis suppress the activation and function of immune cells, including macrophages, dendritic cells, and CD4+ T cells. In this study, we analyzed the course of infection as well as the leishmanicidal effect of intralesional UTP treatment in L. amazonensis-infected BALB/c mice. We found that UTP treatment reduced the parasitic load in both footpad and lymph node sites of infection...
June 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29626320/uric-acid-levels-are-associated-with-endothelial-dysfunction-and-severity-of-coronary-atherosclerosis-during-a-first-episode-of-acute-coronary-syndrome
#8
Mélanie Gaubert, Marion Marlinge, Marine Alessandrini, Marc Laine, Laurent Bonello, Julien Fromonot, Jennifer Cautela, Franck Thuny, Jeremie Barraud, Giovanna Mottola, Pascal Rossi, Emmanuel Fenouillet, Jean Ruf, Régis Guieu, Franck Paganelli
The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point...
June 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29619754/the-involvement-of-purinergic-signalling-in-obesity
#9
REVIEW
Geoffrey Burnstock, Daniela Gentile
Obesity is a growing worldwide health problem, with an alarming increasing prevalence in developed countries, caused by a dysregulation of energy balance. Currently, no wholly successful pharmacological treatments are available for obesity and related adverse consequences. In recent years, hints obtained from several experimental animal models support the notion that purinergic signalling, acting through ATP-gated ion channels (P2X), G protein-coupled receptors (P2Y) and adenosine receptors (P1), is involved in obesity, both at peripheral and central levels...
June 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29541926/p2x-7-receptor-and-klotho-expressions-in-diabetic-nephropathy-progression
#10
A M Rodrigues, R S Serralha, C Farias, G R Punaro, M J S Fernandes, Elisa Mieko Suemitsu Higa
Diabetes mellitus is characterized by increased levels of reactive oxygen species (ROS), leading to high levels of adenosine triphosphate (ATP) and the activation of purinergic receptors (P2X7 ), which results in cell death. Klotho was recently described as a modulator of oxidative stress and as having anti-apoptotic properties, among others. However, the roles of P2X7 and klotho in the progression of diabetic nephropathy are still unclear. In this context, the aim of the present study was to characterize P2X7 and klotho in several stages of diabetes in rats...
June 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29516286/npp1-is-responsible-for-potent-extracellular-atp-hydrolysis-as-ntpdase1-in-primary-cultured-murine-microglia
#11
Hye Min Lim, Woon Heo, Jung Woo Han, Min Goo Lee, Joo Young Kim
The movement of microglia is regulated mainly by P1 and P2 purinergic receptors, which are activated by various nucleotides and their metabolites. Recently, such purinergic signalling has been spotlighted because of potential roles in the pathophysiologies of neurodegenerative and neuropsychiatric disorders. To understand the characteristics of microglia in relation of P1 and P2 signalling, we investigated the ectoenzymes expressed in microglia. At first, we profiled the expression of all known ectoenzymes in cultured microglia...
June 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29492786/functional-coupling-between-adenosine-a-1-receptors-and-g-proteins-in-rat-and-postmortem-human-brain-membranes-determined-with-conventional-guanosine-5-o-3-35-s-thio-triphosphate-35-s-gtp%C3%AE-s-binding-or-35-s-gtp%C3%AE-s-immunoprecipitation-assay
#12
Yuji Odagaki, Masakazu Kinoshita, Toshio Ota, J Javier Meana, Luis F Callado, Isao Matsuoka, Jesús A García-Sevilla
Adenosine signaling plays a complex role in multiple physiological processes in the brain, and its dysfunction has been implicated in pathophysiology of neuropsychiatric diseases such as schizophrenia and affective disorders. In the present study, the coupling between adenosine A1 receptor and G-protein was assessed by means of two [35 S]GTPγS binding assays, i.e., conventional filtration method and [35 S]GTPγS binding/immunoprecipitation in rat and human brain membranes. The latter method provides information about adenosine A1 receptor-mediated Gαi-3 activation in rat as well as human brain membranes...
June 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29332180/cd39-adenosinergic-axis-in-renal-pathophysiology-and-therapeutics
#13
REVIEW
Bellamkonda K Kishore, Simon C Robson, Karen M Dwyer
Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits many crucial biological functions. Extracellular ATP is sequentially hydrolyzed to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular adenosine interacts with P1 receptors and often opposes the effects of P2 receptor activation. The balance between extracellular ATP and adenosine in the blood and extracellular fluid is regulated chiefly by the activities of CD39 and CD73, which constitute the CD39-adenosinergic axis...
June 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29290027/n-terminal-tagging-of-human-p2x7-receptor-disturbs-calcium-influx-and-dye-uptake
#14
Karin Dreisig, Nikolaj Pagh Kristensen, Maja Wallentin Dommer, Niklas Rye Jørgensen, Birgitte Rahbek Kornum
The P2X7 receptor is a frequently studied member of the purinergic receptor family signalling via channel opening and membrane pore formation. Fluorescent imaging is an important molecular method for studying cellular receptor expression and localization. Fusion of receptors to fluorescent proteins might cause major functional changes and requires careful functional evaluation such as has been done for the rat P2X7 receptor. This study examines fusion constructs of the human P2X7 receptor. We assessed surface expression, channel opening with calcium influx, and pore formation using YO-PRO-1 dye uptake in response to BzATP stimulation in transfected cells...
March 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29236227/loss-of-vascular-expression-of-nucleoside-triphosphate-diphosphohydrolase-1-cd39-in-hypertension
#15
Charlotte Roy, Julie Tabiasco, Antoine Caillon, Yves Delneste, Jean Merot, Julie Favre, Anne Laure Guihot, Ludovic Martin, Daniele C Nascimento, Bernhard Ryffel, Simon C Robson, Jean Sévigny, Daniel Henrion, Gilles Kauffenstein
Ectonucleoside triphosphate diphosphohydrolase-1, the major vascular/immune ectonucleotidase, exerts anti-thrombotic and immunomodulatory actions by hydrolyzing extracellular nucleotides (danger signals). Hypertension is characterized by vascular wall remodeling, endothelial dysfunction, and immune infiltration. Here our aim was to investigate the impact of arterial hypertension on CD39 expression and activity in mice. Arterial expression of CD39 was determined by reverse transcription quantitative real-time PCR in experimental models of hypertension, including angiotensin II (AngII)-treated mice (1 mg/kg/day, 21 days), deoxycorticosterone acetate-salt mice (1% salt and uninephrectomy, 21 days), and spontaneously hypertensive rats...
March 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29188550/udp-induced-relaxation-is-enhanced-in-aorta-from-female-obese-otsuka-long-evans-tokushima-fatty-rats
#16
Shota Kobayashi, Takayuki Matsumoto, Makoto Ando, Maika Iguchi, Shun Watanabe, Kumiko Taguchi, Tsuneo Kobayashi
Uridine 5'-diphosphate (UDP) plays an important role in controlling vascular tone; however, UDP-mediated response in metabolic syndromes, including obesity and type 2 diabetes in females, remains unclear. In this study, we investigated UDP-mediated response in the aorta of female obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. In OLETF rat aortas precontracted by phenylephrine (PE) (vs. LETO), (1) UDP-induced relaxation was increased, whereas acetylcholine (ACh)-induced relaxation was decreased; (2) no UDP- or ACh-induced relaxations were observed in endothelial denudation, whereas UDP-induced small contraction was observed; and (3) NG -nitro-L-arginine [L-NNA, a nitric oxide (NO) synthase inhibitor] eliminated UDP-induced relaxation and small contraction, whereas caused contrasting responses by ACh, including slight relaxations (LETO) and contractions (OLETF)...
March 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29170977/species-differences-and-mechanism-of-action-of-a-3-adenosine-receptor-allosteric-modulators
#17
Lili Du, Zhan-Guo Gao, Silvia Paoletta, Tina C Wan, Elizabeth T Gizewski, Samantha Barbour, Jacobus P D van Veldhoven, Adriaan P IJzerman, Kenneth A Jacobson, John A Auchampach
Activity of the A3 adenosine receptor (AR) allosteric modulators LUF6000 (2-cyclohexyl-N-(3,4-dichlorophenyl)-1H-imidazo [4,5-c]quinolin-4-amine) and LUF6096 (N-{2-[(3,4-dichlorophenyl)amino]quinolin-4-yl}cyclohexanecarbox-amide) was compared at four A3 AR species homologs used in preclinical drug development. In guanosine 5'-[γ-[35 S]thio]triphosphate ([35 S]GTPγS) binding assays with cell membranes isolated from human embryonic kidney cells stably expressing recombinant A3 ARs, both modulators substantially enhanced agonist efficacy at human, dog, and rabbit A3 ARs but provided only weak activity at mouse A3 ARs...
March 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29164451/the-potential-of-p2x7-receptors-as-a-therapeutic-target-including-inflammation-and-tumour-progression
#18
REVIEW
Geoffrey Burnstock, Gillian E Knight
Seven P2X ion channel nucleotide receptor subtypes have been cloned and characterised. P2X7 receptors (P2X7R) are unusual in that there are extra amino acids in the intracellular C terminus. Low concentrations of ATP open cation channels sometimes leading to cell proliferation, whereas high concentrations of ATP open large pores that release inflammatory cytokines and can lead to apoptotic cell death. Since many diseases involve inflammation and immune responses, and the P2X7R regulates inflammation, there has been recent interest in the pathophysiological roles of P2X7R and the potential of P2X7R antagonists to treat a variety of diseases...
March 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29159762/p2y-12-receptor-upregulation-in-satellite-glial-cells-is-involved-in-neuropathic-pain-induced-by-hiv-glycoprotein-120-and-2-3-dideoxycytidine
#19
Zhihua Yi, Lihui Xie, Congfa Zhou, Huilong Yuan, Shuai Ouyang, Zhi Fang, Shanhong Zhao, Tianyu Jia, Lifang Zou, Shouyu Wang, Yun Xue, Bing Wu, Yun Gao, Guilin Li, Shuangmei Liu, Hong Xu, Changshui Xu, Chunping Zhang, Shangdong Liang
The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2',3'-dideoxycytidine)...
March 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29134411/distinct-roles-of-ecto-nucleoside-triphosphate-diphosphohydrolase-2-ntpdase2-in-liver-regeneration-and-fibrosis
#20
Linda Feldbrügge, Z Gordon Jiang, Eva Csizmadia, Shuji Mitsuhashi, Stephanie Tran, Eric U Yee, Sonja Rothweiler, Kahini A Vaid, Jean Sévigny, Moritz Schmelzle, Yury V Popov, Simon C Robson
Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) are cell surface-located transmembrane ecto-enzymes of the CD39 superfamily which regulate inflammation and tissue repair by catalyzing the phosphohydrolysis of extracellular nucleotides and modulating purinergic signaling. In the liver, NTPDase2 is reportedly expressed on portal fibroblasts, but its functional role in regulating tissue regeneration and fibrosis is incompletely understood. Here, we studied the role of NTPDase2 in several models of liver injury using global knockout mice...
March 2018: Purinergic Signalling
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