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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
#1
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
#2
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...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404687/selective-calcium-dependent-inhibition-of-atp-gated-p2x3-receptors-by-bisphosphonates-induced-endogenous-atp-analogue-apppi
#3
Yevheniia Ishchenko, Anastasia Shakirzyanova, Raisa Giniatullina, Andrei Skorinkin, Geneviev Bart, Petri Turhanen, Jorma Maatta, Jukka Monkkonen, 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 pathological process. Nitrogen-containing bisphosphonates (NBP) are efficiently used to treat bone-cancers and metastases. NBP, apart from their toxic effect on cancer cells, also provide analgesia via poorly understood mechanisms. We have previously shown, that NBP, by inhibiting the mevalonate pathway, induced the formation of the novel ATP-analogues such as ApppI which can potentially be involved in NBP analgesia...
April 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28393021/edge-detection-and-mathematic-fitting-for-corneal-surface-with-matlab-software
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28361417/participation-of-purinergic-p2x-receptors-in-the-thermoregulatory-response-to-cooling
#7
T V Kozyreva, E S Meyta, V P Kozaruk
We studied the role of purinergic P2X receptors in the body response to cooling. In experiments on rats, P2X receptor antagonist PPADS was administered in different modes, which resulted in changes of different characteristics of the thermoregulatory response to cold. Iontophoresis of P2X antagonist into the skin decreased the thermal thresholds of all thermoregulatory responses to cooling, which can attest to a modulating effect of P2X receptors on peripheral thermosensitive afferents. Intraperitoneal administration of P2X antagonist suppressed thermoregulatory activity of skeletal muscles (shivering) developing during cooling without changing the thresholds of thermoregulatory responses...
March 30, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28360100/trans-fatty-acids-promote-proinflammatory-signaling-and-cell-death-by-stimulating-the-apoptosis-signal-regulating-kinase-1-ask1-p38-pathway
#8
Yusuke Hirata, Miki Takahashi, Yuki Kudoh, Kuniyuki Kano, Hiroki Kawana, Kumiko Makide, Yasuharu Shinoda, Yasushi Yabuki, Kohji Fukunaga, Junken Aoki, Takuya Noguchi, Atsushi Matsuzawa
Food-borne trans-fatty acids (TFAs) are mainly produced as byproducts during food manufacture. Recent epidemiological studies have revealed that TFA consumption is a major risk factor for various disorders, including atherosclerosis. However, the underlying mechanisms in this disease etiology are largely unknown. Here, we have shown that TFAs potentiate activation of apoptosis signal-regulating kinase 1 (ASK1) induced by extracellular ATP, a damage-associated molecular pattern (DAMP) leaked from injured cells...
March 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28332633/structural-insights-into-the-nucleotide-base-specificity-of-p2x-receptors
#9
Go Kasuya, Yuichiro Fujiwara, Hisao Tsukamoto, Satoshi Morinaga, Satoshi Ryu, Kazushige Touhara, Ryuichiro Ishitani, Yuji Furutani, Motoyuki Hattori, Osamu Nureki
P2X receptors are trimeric ATP-gated cation channels involved in diverse physiological processes, ranging from muscle contraction to nociception. Despite the recent structure determination of the ATP-bound P2X receptors, the molecular mechanism of the nucleotide base specificity has remained elusive. Here, we present the crystal structure of zebrafish P2X4 in complex with a weak affinity agonist, CTP, together with structure-based electrophysiological and spectroscopic analyses. The CTP-bound structure revealed a hydrogen bond, between the cytosine base and the side chain of the basic residue in the agonist binding site, which mediates the weak but significant affinity for CTP...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302727/intersubunit-physical-couplings-fostered-by-the-left-flipper-domain-facilitate-channel-opening-of-p2x4-receptors
#10
Jin Wang, Liang-Fei Sun, Wen-Wen Cui, Wen-Shan Zhao, Xue-Fei Ma, Bin Li, Yan Liu, Yang Yang, You-Min Hu, Li-Dong Huang, Xiao-Yang Cheng, Lingyong Li, Xiang-Yang Lu, Yun Tian, Ye Yu
P2X receptors are ATP-gated trimeric channels with important roles in diverse pathophysiological functions. A detailed understanding of the mechanism underlying the gating process of these receptors is thus fundamentally important and may open new therapeutic avenues. The left flipper (LF) domain of P2X receptors is a flexible loop structure and its coordinated motions together with the dorsal fin (DF) domain are crucial for the channel gating of the P2X receptors. However, the mechanism underlying the crucial role of the LF domain in the channel gating remains obscure...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28289489/glioactive-atp-controls-bdnf-recycling-in-cortical-astrocytes
#11
Beatrice Vignoli, Marco Canossa
We have recently reported that long-term memory retention requires synaptic glia for proBDNF uptake and recycling. Through the recycling course, glial cells release endocytic BDNF, a mechanism that is activated in response to glutamate via AMPA and mGluRI/II receptors. Cortical astrocytes express receptors for many different transmitters suggesting for a complex signaling controlling endocytic BDNF secretion. Here, we demonstrated that the extracellular nucleotide ATP, activating P2X and P2Y receptors, regulates endocytic BDNF secretion in cultured astrocytes...
2017: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/28284836/exciting-and-not-so-exciting-roles-of-pannexins
#12
REVIEW
Eliana Scemes, Jana Velíšková
It is the current view that purinergic signaling regulates many physiological functions. Pannexin1 (Panx1), a member of the gap junction family of proteins is an ATP releasing channel that plays important physio-pathological roles in various tissues, including the CNS. Upon binding to purinergic receptors expressed in neural cells, ATP triggers cellular responses including increased cell proliferation, cell morphology changes, release of cytokines, and regulation of neuronal excitability via release of glutamate, GABA and ATP itself...
March 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28280004/connexin-purinergic-signaling-in-enteric-glia-mediates-the-prolonged-effect-of-morphine-on-constipation
#13
Sukhada Bhave, Aravind Gade, Minho Kang, Kurt F Hauser, William L Dewey, Hamid I Akbarali
Morphine is one of the most widely used drugs for the treatment of pain. However, side effects, including persistent constipation and antinociceptive tolerance limit its clinical efficacy. Prolonged morphine treatment results in a "leaky" gut predisposing to colonic inflammation that is facilitated by microbial dysbiosis and associated bacterial translocation. In this study, we examined the role of enteric glia in mediating this secondary inflammatory response to prolonged treatment with morphine. We found that purinergic P2X receptor activity was significantly enhanced in enteric glia that were isolated from mice with long-term morphine treatment (in vivo) but not upon direct exposure of glia to morphine (in vitro)...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28279755/purinergic-p2-receptors-in-the-paraventricular-nucleus-of-the-hypothalamus-are-involved-in-hyperosmotic-induced-sympathoexcitation
#14
H C Ferreira-Neto, I M R Ribeiro, T S Moreira, S T Yao, V R Antunes
Increases in plasma osmolality activates the paraventricular nucleus of the hypothalamus (PVN) which in turn mounts a physiological response by increasing the release of arginine vasopressin and sympathetic nerve activity to end organs such as the kidney. The PVN expresses an abundance of purinergic receptors including P2X2 receptors. In the present study, we sought to determine (1) whether P2X2-expressing PVN neurons are activated by hypertonic saline or hypertonic mannitol and (2) what effects P2X receptor blockade has on sympathetic nerve activation mediated by a hyperosmotic stimulus...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28267198/serotonergic-transmission-at-merkel-discs-modulation-by-exogenously-applied-chemical-messengers-and-involvement-of-ih-currents
#15
Weipang Chang, Hirosato Kanda, Ryo Ikeda, Jennifer Ling, Jianguo G Gu
The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ-afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings. In the present study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers...
March 7, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28235784/localization-of-the-gate-and-selectivity-filter-of-the-full-length-p2x7-receptor
#16
Anja Pippel, Michaela Stolz, Ronja Woltersdorf, Achim Kless, Günther Schmalzing, Fritz Markwardt
The P2X7 receptor (P2X7R) belongs to the P2X family of ATP-gated cation channels. P2X7Rs are expressed in epithelial cells, leukocytes, and microglia, and they play important roles in immunological and inflammatory processes. P2X7Rs are obligate homotrimers, with each subunit having two transmembrane helices, TM1 and TM2. Structural and functional data regarding the P2X2 and P2X4 receptors indicate that the central trihelical TM2 bundle forms the intrinsic transmembrane channel of P2X receptors. Here, we studied the accessibility of single cysteines substituted along the pre-TM2 and TM2 helix (residues 327-357) of the P2X7R using as readouts (i) the covalent maleimide fluorescence accessibility of the surface-bound P2X7R and (ii) covalent modulation of macroscopic and single-channel currents using extracellularly and intracellularly applied methanethiosulfonate (MTS) reagents...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28224484/introduction-to-the-special-issue-on-purinergic-receptors
#17
Geoffrey Burnstock
In this Introduction to the series of papers that follow about purinergic receptors, there is a brief history of the discovery of purinergic signalling, the identity of purinoceptors and the current recognition of P1, P2X and P2Y subtypes. An account of key functions mediated by purinoceptors follows, including examples of both short-term and long-term (trophic) signalling and a table showing the selective agonists and antagonists for the purinoceptor subtypes. References to evolution and roles of purinoceptors in pathological conditions are also presented...
February 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28209758/atorvastatin-decreases-hbx-induced-phospho-akt-in-hepatocytes-via-p2x-receptors
#18
Aram Ghalali, Javier Martin-Renedo, Johan Hogberg, Ulla Stenius
Hepatocellular carcinoma (HCC) is rated as the fifth most common malignancy and third in cancer related deaths worldwide. Statins, HMG-CoA reductase inhibitors, are potent cholesterol lowering drugs and recent epidemiological evidence suggests that statins prevent aggressive HCC development. Previous experiments revealed that statins downregulate phosphorylated Akt (pAkt). Here, it is demonstrated that atorvastatin decreases nuclear pAkt levels in pancreatic and lung cancer cell lines within minutes and this rapid effect is mediated by the purinergic P2X receptors...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28179439/tussive-challenge-with-atp-and-amp-does-it-reveal-cough-hypersensitivity
#19
Helen Elizabeth Fowles, Tim Rowland, Caroline Wright, Alyn Morice
Recent studies have demonstrated that blockade of P2X3 ATP receptors can profoundly inhibit chronic cough. We have considered whether inhaled ATP produces a tussive response and whether chronic cough patients are hypersensitive to inhaled ATP compared to healthy volunteers.A standardised inhalational cough challenge was performed with ATP and AMP. We randomised 20 healthy volunteers and 20 chronic cough patients as to the order of challenges. The concentration of challenge solution causing at least five coughs (C5) was compared for ATP and AMP...
February 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28174542/p2x-receptors-inhibit-nacl-absorption-in-mtal-independently-of-nitric-oxide
#20
Samuel L Svendsen, Søren Isidor, Helle A Praetorius, Jens Leipziger
Activation of basolateral P2X receptors markedly reduces NaCl absorption in mouse medullary thick ascending limb (mTAL). Here we tested the role of nitric oxide (NO) in the ATP-mediated (P2X) transport inhibition. We used isolated, perfused mTALs from mice to electrically measure NaCl absorption. By microelectrodes we determined the transepithelial voltage (Vte) and transepithelial resistance (Rte). Via these two parameters, we calculated the equivalent short circuit current, I'sc as a measure of the transepithelial Na(+) absorption...
2017: Frontiers in Physiology
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