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https://www.readbyqxmd.com/read/28616989/reconstructed-serine288-in-the-left-flipper-region-of-rat-p2x7-receptor-stabilizes-non-sensitized-states
#1
Yevheniia Ishchenko, Nataliia Novosolova, Kamil Khafizov, Genevieve Bart, Arina Timonina, Dmitriy Fayuk, Andrei Skorinkin, Rashid Giniatullin
Serine 275, a conserved residue of the left flipper region of ATP-gated P2X3 receptors, plays a key role in both agonist binding and receptor desensitization. It is conserved in most of the P2X receptors except P2X7 and P2X6. By combining experimental patch-clamp and modelling approaches, we explored the role of the corresponding residue in rat P2X7 receptor (rP2X7) by replacing phenylalanine in the position 288 with serine and characterizing the membrane currents generated by either WT or mutated rP2X7 receptor...
June 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28615626/neuronal-p2x7-receptor-induced-reactive-oxygen-species-production-contributes-to-nociceptive-behavior-in-mice
#2
Frances M Munoz, Ruby Gao, Yuzhen Tian, Brian A Henstenburg, James E Barrett, Huijuan Hu
ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen species (ROS) in macrophages and microglia. However, the role of ROS in P2X7R-induced pain remains unexplored. Here, we investigated the downstream effects of neuronal P2X7R activation in the spinal cord. We found that ATP induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) and P2X7R antagonist A438079...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588493/p2x4-receptor-function-in-the-nervous-system-and-current-breakthroughs-in-pharmacology
#3
REVIEW
Leanne Stokes, Janice A Layhadi, Lucka Bibic, Kshitija Dhuna, Samuel J Fountain
Adenosine 5'-triphosphate is a well-known extracellular signaling molecule and neurotransmitter known to activate purinergic P2X receptors. Information has been elucidated about the structure and gating of P2X channels following the determination of the crystal structure of P2X4 (zebrafish), however, there is still much to discover regarding the role of this receptor in the central nervous system (CNS). In this review we provide an overview of what is known about P2X4 expression in the CNS and discuss evidence for pathophysiological roles in neuroinflammation and neuropathic pain...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28573491/p2x7-receptor-large-pore-signaling-in-avian-m%C3%A3-ller-glial-cells
#4
Robson X Faria, Hercules R Freitas, Ricardo A M Reis
ATP is a pleiotropic molecule that promotes extra- and intracellular signaling to regulate numerous functions. This nucleotide activates purine and pyrimidine receptors at the plasma membrane, categorized as ionotropic P2X or G-protein-coupled receptor (GPCR) P2Y receptors. P2X are ligand-gated ion channel receptors, expressed in both retinal neurons and Müller cells leading to neuron-glia communication, calcium waves and neurovascular coupling. However, how P2X pore is formed upon ATP activation and how signaling pathways regulates the complex is still a matter of controversy...
June 1, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28555330/the-p2y1-receptor-mediated-leukocyte-adhesion-to-endothelial-cells-is-inhibited-by-melatonin
#5
Tassya Cataldi Cardoso, Thaís Emanuelle Pompeu, Claudia Lucia Martins Silva
Extracellular ATP (released by endothelial and immune cells) and its metabolite ADP are important pro-inflammatory mediators via the activation of purinergic P2 receptors (P2Y and P2X), which represent potential new targets for anti-inflammatory therapy. Endothelial P2Y1 receptor (P2Y1R) induces endothelial cell activation triggering leukocyte adhesion. A number of data have implicated melatonin as a modulator of immunity, inflammation, and endothelial cell function, but to date no studies have investigated whether melatonin modulates endothelial P2YR signaling...
May 29, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28547658/time-of-day-dependent-expression-of-purinergic-receptors-in-mouse-suprachiasmatic-nucleus
#6
Julian Lommen, Anna Stahr, Marc Ingenwerth, Amira A H Ali, Charlotte von Gall
Purinergic P2X and P2Y receptors are involved in mediating intercellular signalling via purines such as adenosine triphosphate (ATP). P2X and P2Y receptors have been implicated in numerous body functions including learning, memory and sleep. All of these body functions show time-of-day-dependent variations controlled by the master circadian oscillator located in the suprachiasmatic nucleus (SCN). Evidence exists for a role of purinergic signalling in intercellular coupling within SCN. However, few studies have been performed on the expression of purinergic receptors in SCN...
May 26, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28534085/atp-induced-ca-2-signalling-mechanisms-in-the-regulation-of-mesenchymal-stem-cell-migration
#7
REVIEW
Lin-Hua Jiang, Fatema Mousawi, Xuebin Yang, Sėbastien Roger
The ability of cells to migrate to the destined tissues or lesions is crucial for physiological processes from tissue morphogenesis, homeostasis and immune responses, and also for stem cell-based regenerative medicines. Cytosolic Ca(2+) is a primary second messenger in the control and regulation of a wide range of cell functions including cell migration. Extracellular ATP, together with the cognate receptors on the cell surface, ligand-gated ion channel P2X receptors and a subset of G-protein-coupled P2Y receptors, represents common autocrine and/or paracrine Ca(2+) signalling mechanisms...
May 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28530470/cd73-controls-extracellular-adenosine-generation-in-the-trigeminal-nociceptive-nerves
#8
X Liu, L Ma, S Zhang, Y Ren, R T Dirksen
Purinergic signaling is involved in pain generation and modulation in the nociceptive sensory nervous system. Adenosine triphosphate (ATP) induces pain via activation of ionotropic P2X receptors while adenosine mediates analgesia via activation of metabotropic P1 receptors. These purinergic signaling are determined by ecto-nucleotidases that control ATP degradation and adenosine generation. Using enzymatic histochemistry, we detected ecto-AMPase activity in dental pulp, trigeminal ganglia (TG) neurons, and their nerve fibers...
June 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28528728/spontaneous-calcium-waves-in-the-developing-enteric-nervous-system
#9
Marlene M Hao, Annette J Bergner, Caroline S Hirst, Lincon A Stamp, Franca Casagranda, Joel C Bornstein, Werend Boesmans, Pieter Vanden Berghe, Heather M Young
The enteric nervous system (ENS) is an extensive network of neurons in the gut wall that arises from neural crest-derived cells. Like other populations of neural crest cells, it is known that enteric neural crest-derived cells (ENCCs) influence the behaviour of each other and therefore must communicate. However, little is known about how ENCCs communicate with each other. In this study, we used Ca(2+) imaging to examine communication between ENCCs in the embryonic gut, using mice where ENCCs express a genetically-encoded calcium indicator...
May 18, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28500314/activation-of-eosinophils-interacting-with-bronchial-epithelial-cells-by-antimicrobial-peptide-ll-37-implications-in-allergic-asthma
#10
Delong Jiao, Chun-Kwok Wong, Miranda Sin-Man Tsang, Ida Miu-Ting Chu, Dehua Liu, Jing Zhu, Man Chu, Christopher Wai-Kei Lam
The role of antimicrobial peptide LL-37 in asthma exacerbation is unclear. Microbial infection, which is the most common inducer of asthma exacerbation, is accompanied by elevated LL-37. The present study found that co-culture of eosinophils and bronchial epithelial cell line BEAS-2B significantly enhanced intercellular adhesion molecule-1 on both cells and CD18 expression on eosinophils upon LL-37 stimulation. IL-6, CXCL8 and CCL4 were substantially released in co-culture in the presence of LL-37. LL-37 triggered the activation of eosinophils interacting with BEAS-2B cells in a P2X purinoceptor 7/epidermal growth factor receptor-dependent manner...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28488084/loop-diuretics-diminish-hemolysis-induced-by-%C3%AE-hemolysin-from-escherichia-coli
#11
Carl Martin Söderström, Steen K Fagerberg, Mette B Brogaard, Jens Leipziger, Marianne Skals, Helle A Praetorius
Uropathogenic Escherichia coli often produce the virulence factor α-hemolysin (HlyA), and the more severe the infection, the likelier it is to isolate HlyA-producing E. coli from patients. HlyA forms pores upon receptor-independent insertion of the toxin into biological membranes and it has been substantiated that HlyA-induced hemolysis is amplified by toxin-induced ATP release and activation of P2X receptors. Thus, hemolysis inflicted by HlyA is a protracted process involving signal transduction. It consists of early, marked cell shrinkage followed by swelling and eventually lysis...
May 9, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28469648/regulation-of-neural-stem-progenitor-cell-functions-by-p2x-and-p2y-receptors
#12
Peter Illes, Patrizia Rubini
No abstract text is available yet for this article.
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28458288/neuropharmacological-study-of-atp-receptors-especially-in-the-relationship-between-glia-and-pain
#13
Kazuhide Inoue
 A growing body of evidence indicates that extracellular ATP released or leaked from nonexcitable cells as well as neurons plays important roles in the regulation of neuronal and glial functions in the entire body through ATP receptors. ATP receptors (ionotropic P2X and metabotropic P2Y receptors) are the most abundant receptor families in living organisms. In the central nervous system, these receptors participate in the synaptic transmission and intercellular communications between neurons and glia. The glia cells are classified into three types: astrocytes; oligodendrocytes; and microglia...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28442564/on-the-permeation-of-large-organic-cations-through-the-pore-of-atp-gated-p2x-receptors
#14
Mahboubi Harkat, Laurie Peverini, Adrien H Cerdan, Kate Dunning, Juline Beudez, Adeline Martz, Nicolas Calimet, Alexandre Specht, Marco Cecchini, Thierry Chataigneau, Thomas Grutter
Pore dilation is thought to be a hallmark of purinergic P2X receptors. The most commonly held view of this unusual process posits that under prolonged ATP exposure the ion pore expands in a striking manner from an initial small-cation conductive state to a dilated state, which allows the passage of larger synthetic cations, such as N-methyl-d-glucamine (NMDG(+)). However, this mechanism is controversial, and the identity of the natural large permeating cations remains elusive. Here, we provide evidence that, contrary to the time-dependent pore dilation model, ATP binding opens an NMDG(+)-permeable channel within milliseconds, with a conductance that remains stable over time...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28428949/p2x1-p2x4-and-p2x7-receptor-knock-out-mice-expose-differential-outcome-of-sepsis-induced-by-%C3%AE-haemolysin-producing-escherichia-coli
#15
Anne-Sofie Greve, Marianne Skals, Steen K Fagerberg, Wulf Tonnus, Svend Ellermann-Eriksen, Richard J Evans, Andreas Linkermann, Helle A Praetorius
α-haemolysin (HlyA)-producing Escherichia coli commonly inflict severe urinary tract infections, including pyelonephritis, which comprises substantial risk for sepsis. In vitro, the cytolytic effect of HlyA is mainly mediated by ATP release through the HlyA pore and subsequent P2X1/P2X7 receptor activation. This amplification of the lytic process is not unique to HlyA but is observed by many other pore-forming proteins including complement-induced haemolysis. Since free hemoglobin in the blood is known to be associated with a worse outcome in sepsis one could speculate that inhibition of P2X receptors would ameliorate the course of sepsis...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28418839/carcinoma-specific-expression-of-p2y11-receptor-and-its-contribution-in-atp-induced-purinergic-signalling-and-cell-migration-in-human-hepatocellular-carcinoma-cells
#16
Madiha Khalid, Lucie Brisson, Menahil Tariq, Yunjie Hao, Roseline Guibon, Gaëlle Fromont, Sharifah Alawieyah Syed Mortadza, Fatema Mousawi, Sobia Manzoor, Sébastien Roger, Lin-Hua Jiang
Extracellular ATP-induced Ca2+ signalling is critical in regulating diverse physiological and disease processes. Emerging evidence suggests high concentrations of extracellular ATP in tumour tissues. In this study, we examined the P2 receptor for ATP-induced Ca2+ signalling in human hepatocellular carcinoma (HCC) cells. Fura-2-based measurements of the intracellular Ca2+ concentration ([Ca2+]i) showed that extracellular ATP induced an increase in the [Ca2+]i in human HCC Huh-7 and HepG2 cells. NF546, a P2Y11 receptor agonist was equally effective in inducing an increase in the [Ca2+]i...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404687/selective-calcium-dependent-inhibition-of-atp-gated-p2x3-receptors-by-bisphosphonate-induced-endogenous-atp-analog-apppi
#17
Yevheniia Ishchenko, Anastasia Shakirzyanova, Raisa Giniatullina, Andrei Skorinkin, Genevieve Bart, Petri Turhanen, Jorma A Määttä, Jukka Mönkkönen, Rashid Giniatullin
Pain is the most unbearable symptom accompanying primary bone cancers and bone metastases. Bone resorptive disorders are often associated with hypercalcemia, contributing to the pathologic process. Nitrogen-containing bisphosphonates (NBPs) are efficiently used to treat bone cancers and metastases. Apart from their toxic effect on cancer cells, NBPs also provide analgesia via poorly understood mechanisms. We previously showed that NBPs, by inhibiting the mevalonate pathway, induced formation of novel ATP analogs such as ApppI [1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) triphosphoric acid diester], which can potentially be involved in NBP analgesia...
June 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28393021/edge-detection-and-mathematic-fitting-for-corneal-surface-with-matlab-software
#18
Yue Di, Mei-Yan Li, Tong Qiao, Na Lu
AIM: To select the optimal edge detection methods to identify the corneal surface, and compare three fitting curve equations with Matlab software. METHODS: Fifteen subjects were recruited. The corneal images from optical coherence tomography (OCT) were imported into Matlab software. Five edge detection methods (Canny, Log, Prewitt, Roberts, Sobel) were used to identify the corneal surface. Then two manual identifying methods (ginput and getpts) were applied to identify the edge coordinates respectively...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28389204/interactions-of-pannexin1-channels-with-purinergic-and-nmda-receptor-channels
#19
REVIEW
Shuo Li, Ivana Bjelobaba, Stanko S Stojilkovic
Pannexins are a three-member family of vertebrate plasma membrane spanning molecules that have homology to the invertebrate gap junction forming proteins, the innexins. However, pannexins do not form gap junctions but operate as plasma membrane channels. The best-characterized member of these proteins, Pannexin1 (Panx1) was suggested to be functionally associated with purinergic P2X and N-methyl-D-aspartate (NMDA) receptor channels. Activation of these receptor channels by their endogenous ligands leads to cross-activation of Panx1 channels...
April 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28377398/il-27-enhances-lps-induced-il-1%C3%AE-in-human-monocytes-and-murine-macrophages
#20
Carlene Petes, Christopher Wynick, Christina Guzzo, Divya Mehta, Sarah Logan, Bruce W Banfield, Sameh Basta, Andrea Cooper, Katrina Gee
IL-27 bridges innate and adaptive immunity by modulating cytokine production from myeloid cells and regulating Th cell differentiation. During bacterial infection, TLR4 triggering by LPS induces IL-27 production by monocytes and macrophages. We have previously shown that IL-27 can prime monocytes for LPS responsiveness by enhancing TLR4 expression and intracellular signaling. If unregulated, this could result in damaging inflammation, whereas on the other hand, this may also provide greater responses by inflammatory processes induced in response to bacterial pathogens...
April 4, 2017: Journal of Leukocyte Biology
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