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https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#1
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905561/anti-hu-antibodies-activate-enteric-and-sensory-neurons
#2
Qin Li, Klaus Michel, Anita Annahazi, Ihsan E Demir, Güralp O Ceyhan, Florian Zeller, Lars Komorowski, Winfried Stöcker, Michael J Beyak, David Grundy, Gianrico Farrugia, Roberto De Giorgio, Michael Schemann
IgG of type 1 anti-neuronal nuclear antibody (ANNA-1, anti-Hu) specificity is a serological marker of paraneoplastic neurological autoimmunity (including enteric/autonomic) usually related to small-cell lung carcinoma. We show here that IgG isolated from such sera and also affinity-purified anti-HuD label enteric neurons and cause an immediate spike discharge in enteric and visceral sensory neurons. Both labelling and activation of enteric neurons was prevented by preincubation with the HuD antigen. Activation of enteric neurons was inhibited by the nicotinic receptor antagonists hexamethonium and dihydro-β-erythroidine and reduced by the P2X antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid (PPADS) but not by the 5-HT3 antagonist tropisetron or the N-type Ca-channel blocker ω-Conotoxin GVIA...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27877078/activation-of-the-cxcl16-cxcr6-pathway-by-inflammation-contributes-to-atherosclerosis-in-patients-with-end-stage-renal-disease
#3
Ze Bo Hu, Yan Chen, Yu Xiang Gong, Min Gao, Yang Zhang, Gui Hua Wang, Ri Ning Tang, Hong Liu, Bi Cheng Liu, Kun Ling Ma
Background: Chronic inflammation plays a critical role in the progression of atherosclerosis (AS). This study aimed to determine the effects of the CXC chemokine ligand 16 (CXCL16)/CXC chemokine receptor 6 (CXCR6) pathway on cholesterol accumulation in the radial arteries of end-stage renal disease (ESRD) patients with concomitant microinflammation and to further investigate the potential effects of the purinergic receptor P2X ligand-gated ion channel 7 (P2X7R). Methods: Forty-three ESRD patients were divided into the control group (n=17) and the inflamed group (n=26) based on plasma C-reactive protein (CRP) levels...
2016: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/27871906/adenosine-but-not-guanosine-protects-vaginal-epithelial-cells-from-trichomonas-vaginalis-cytotoxicity
#4
Camila Braz Menezes, Amanda Piccoli Frasson, Lucia Collares Meirelles, Tiana Tasca
Trichomonas vaginalis causes the most common non-viral sexually transmitted disease worldwide. The cytoadherence and cytotoxicity upon the vaginal epithelial cells are crucial for the infection. Extracellular nucleotides are released during cell damage and, along with their nucleosides, can activate purinoceptors. The opposing effects of nucleotides versus nucleosides are regulated by ectonucleotidases. Herein we evaluated the hemolysis and cytolysis induced by T. vaginalis, as well as the extracellular nucleotide hydrolysis along with the effects mediated by nucleotides and nucleosides on cytotoxicity...
November 18, 2016: Microbes and Infection
https://www.readbyqxmd.com/read/27863396/p2rx4-deficiency-in-mice-alleviates-allergen-induced-airway-inflammation
#5
Andreas Zech, Benjamin Wiesler, Cemil Korcan Ayata, Tilmann Schlaich, Thorsten Dürk, Madelon Hoßfeld, Nicolas Ehrat, Sanja Cicko, Marco Idzko
Compelling evidences point out a crucial role for extracellular nucleotides such as adenosine triphosphate (ATP) during inflammatory conditions. Once released into the extracellular space, ATP modulates migration, maturation and function of various inflammatory cells via activating of purinergic receptors of the P2Y- and P2X- family. P2RX4 is an ATP-guided ion channel expressed on structural cells such as alveolar epithelial and smooth muscle cells as well as inflammatory cells including macrophages, dendritic cells (DCs) and T cells...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27802438/bradykinin-contributes-to-sympathetic-and-pressor-responses-evoked-by-activation-of-skeletal-muscle-afferents-p2x-in-heart-failure
#6
Jihong Xing, Jianhua Li
BACKGROUND/AIMS: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA) and blood pressure (BP) responses during static exercise in heart failure (HF). In this study, we examined engagement of bradykinin (BK) in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG) neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27780585/purinergic-signaling-in-kidney-disease
#7
REVIEW
Robert I Menzies, Frederick W Tam, Robert J Unwin, Matthew A Bailey
Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP-activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP, and UDP in the case of P2 or adenosine for P1. Renal P2 receptors influence both vascular contractility and tubular function...
October 22, 2016: Kidney International
https://www.readbyqxmd.com/read/27778376/post-injury-bladder-management-strategy-influences-lower-urinary-tract-dysfunction-in-the-mouse-model-of-spinal-cord-injury
#8
Naoki Wada, Takahiro Shimizu, Shun Takai, Nobutaka Shimizu, Anthony J Kanai, Pradeep Tyagi, Hidehiro Kakizaki, Naoki Yoshimura
AIMS: To examine the effects of a different number of daily bladder squeezes on bladder dysfunction in mice with spinal cord injury (SCI). METHODS: Spinal cord was transected at the Th8/9 in female C57BL/6N mice. Their bladders were manually squeezed to eliminate urine inside every day for 4 weeks. The mice were divided into three groups depending on the number of bladder squeezes; A: once daily, B: twice daily, C: three times daily. Four weeks after transection, single-filling cystometry were performed under an awake condition...
October 24, 2016: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/27766552/synthesis-characterization-and-in-vitro-evaluation-of-the-selective-p2y2-receptor-antagonist-ar-c118925
#9
Muhammad Rafehi, Joachim C Burbiel, Isaac Y Attah, Aliaa Abdelrahman, Christa E Müller
The Gq protein-coupled, ATP- and UTP-activated P2Y2 receptor is a potential drug target for a range of different disorders, including tumor metastasis, inflammation, atherosclerosis, kidney disorders, and osteoporosis, but pharmacological studies are impeded by the limited availability of suitable antagonists. One of the most potent and selective antagonists is the thiouracil derivative AR-C118925. However, this compound was until recently not commercially available and little is known about its properties...
October 20, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27757785/2-3-o-substituted-atp-derivatives-as-potent-antagonists-of-purinergic-p2x3-receptors-and-potential-analgesic-agents
#10
Diego Dal Ben, Anna Marchenkova, Ajiroghene Thomas, Catia Lambertucci, Andrea Spinaci, Gabriella Marucci, Andrea Nistri, Rosaria Volpini
Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized...
October 18, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27754822/role-of-purines-in-m%C3%A3-ller-glia
#11
Andreas Reichenbach, Andreas Bringmann
Müller glia, the principal macroglia of the retina, express diverse subtypes of adenosine and metabotropic purinergic (P2Y) receptors. Müller cells of several species, including man, also express ionotropic P2X7 receptors. ATP is liberated from Müller cells after activation of metabotropic glutamate receptors and during osmotic and mechanical induction of membrane stretch; adenosine is released through equilibrative nucleoside transporters. Müller cell-derived purines modulate the neuronal activity and have autocrine effects, for example, induction of glial calcium waves and regulation of the cellular volume...
October 2016: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27748894/blocking-of-the-p2x7-receptor-inhibits-the-activation-of-the-mmp-13-and-nf-%C3%AE%C2%BAb-pathways-in-the-cartilage-tissue-of-rats-with-osteoarthritis
#12
Hongbo Hu, Baohui Yang, Yumin Li, Subin Zhang, Zheng Li
P2X purinoceptor 7 (P2X7) receptor (P2X7R) is known to play a significant role in inflammation and pain-causing diseases, including osteoarthritis (OA). However, the mechanisms of action of P2X7R and its role in OA remain unclear. The articular cartilage is the crucial region in which pathological changes occur in OA, involving the dysregulation of degradation and maintenance mechanisms. In this study, we aimed to reveal the molecular mechanisms of action of P2X7R in articular cartilage in OA-induced pain and inflammation by using AZD9056, an antagonist of P2X7R...
October 13, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27724045/p2x7-receptor-antagonists-a-patent-review-2010-2015
#13
Jin-Hee Park, Yong-Chul Kim
The P2X7 receptor (P2X7R) is a unique subtype among the family of seven purinergic P2X receptors, which are ATP-gated non-selective cation channels. P2X7R has been reported to have pathological roles in various diseases, including autoimmune diseases such as arthritis and inflammatory bowel disease, neurodegenerative diseases, chronic pain, mood disorders and cancers. Therefore, many pharmaceutical companies have endeavored to develop a clinical candidate targeting P2X7R. Areas covered: This review provides a summary of various patents on chemicals and biologics and their clinical use published between 2010 and 2015...
October 10, 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27720754/physiological-contribution-of-p2x-receptors-in-postreceptoral-signal-processing-in-the-mouse-retina
#14
Sho Ichinohe, Toshiyuki Ishii, Hiroshi Takahashi, Makoto Kaneda
ATP activates P2X receptors and acts as a neurotransmitter in the nervous system. We have previously reported that P2X receptors modulate the firing rate of retinal ganglion cells. Since many subtypes of P2X receptors are distributed in the mouse retina, it is likely that the modulatory effects of P2X receptor-mediated signaling can occur at multiple synaptic levels in the retina. In this study, we investigated whether P2X receptors expressed between the photoreceptor layer and the inner nuclear layer in the mouse retina were physiologically functional, by electroretinography (ERG)...
October 5, 2016: Neuroscience Research
https://www.readbyqxmd.com/read/27682519/influence-of-p2x-receptors-on-renal-medullary-circulation-is-not-altered-by-angiotensin-ii-pretreatment
#15
Marta Kuczeriszka, Leszek Dobrowolski, Agnieszka Walkowska, Janusz Sadowski
BACKGROUND: Purine P2X and P2Y receptors (P2-R) are involved in control of renal circulation, especially in the medulla, wherein they appear to interact with angiotensin II (Ang II). Our experimental approach enabled examination of interaction with Ang II per se, in the absence of blood pressure elevation. In this whole-kidney functional study we focused on the influence of P2X1-R on perfusion of the renal medulla. METHODS: Acute experiments were conducted with normal rats, untreated or subjected to two weeks' infusion of Ang II (osmotic minipumps)...
August 1, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27667006/how-azobenzene-photoswitches-restore-visual-responses-to-the-blind-retina
#16
Ivan Tochitsky, Zachary Helft, Victor Meseguer, Russell B Fletcher, Kirstan A Vessey, Michael Telias, Bristol Denlinger, Jonatan Malis, Erica L Fletcher, Richard H Kramer
Azobenzene photoswitches confer light sensitivity onto retinal ganglion cells (RGCs) in blind mice, making these compounds promising candidates as vision-restoring drugs in humans with degenerative blindness. Remarkably, photosensitization manifests only in animals with photoreceptor degeneration and is absent from those with intact rods and cones. Here we show that P2X receptors mediate the entry of photoswitches into RGCs, where they associate with voltage-gated ion channels, enabling light to control action-potential firing...
October 5, 2016: Neuron
https://www.readbyqxmd.com/read/27666820/long-non-coding-rnas-regulate-effects-of-%C3%AE-crystallin-b2-on-mouse-ovary-development
#17
Qian Gao, Hanxiao Ren, Mingkun Chen, Ziguang Niu, Haibo Tao, Yin Jia, Jianrong Zhang, Wenjie Li
β-crystallin B2 (CRYBB2) knockout mice exhibit morphological and functional abnormalities in the ovary. Long non‑coding RNAs (lncRNAs) regulate gene transcription and translation, and epigenetic modification of genomic DNA. The present study investigated the role of lncRNAs in mediating the effects of CRYBB2 in the regulation of ovary development in mice. In the current study, ovary tissues from wild‑type (WT) and CRYBB2 knockout mice were subjected to lncRNA and mRNA microarray profiling. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to group the differentially expressed lncRNAs into regulated gene pathways and functions...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27641912/atp-induced-il-1%C3%AE-secretion-is-selectively-impaired-in-microglia-as-compared-to-hematopoietic-macrophages
#18
Saskia Maria Burm, Ella Alwine Zuiderwijk-Sick, Paola Massiel Weert, Jeffrey John Bajramovic
Under stressful conditions nucleotides are released from dying cells into the extracellular space, where they can bind to purinergic P2X and P2Y receptors. High concentrations of extracellular ATP in particular induce P2X7-mediated signaling, which leads to inflammasome activation. This in turn leads to the processing and secretion of pro-inflammatory cytokines, like interleukin (IL)-1β. During neurodegenerative diseases, innate immune responses are shaped by microglia and we have previously identified microglia-specific features of inflammasome-mediated responses...
September 19, 2016: Glia
https://www.readbyqxmd.com/read/27640997/atp-from-synaptic-terminals-and-astrocytes-regulates-nmda-receptors-and-synaptic-plasticity-through-psd-95-multi-protein-complex
#19
U Lalo, O Palygin, A Verkhratsky, S G N Grant, Y Pankratov
Recent studies highlighted the importance of astrocyte-secreted molecules, such as ATP, for the slow modulation of synaptic transmission in central neurones. Biophysical mechanisms underlying the impact of gliotransmitters on the strength of individual synapse remain, however, unclear. Here we show that purinergic P2X receptors can bring significant contribution to the signalling in the individual synaptic boutons. ATP released from astrocytes facilitates a recruitment of P2X receptors into excitatory synapses by Ca(2+)-dependent mechanism...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27638862/calpain-activity-is-essential-for-atp-driven-unconventional-vesicle-mediated-protein-secretion-and-inflammasome-activation-in-human-macrophages
#20
Elina Välimäki, Wojciech Cypryk, Juhani Virkanen, Katariina Nurmi, Pauli M Turunen, Kari K Eklund, Karl E Åkerman, Tuula A Nyman, Sampsa Matikainen
Extracellular ATP is an endogenous danger signal that is known to activate inflammatory responses in innate immune cells, including macrophages. Activated macrophages start to secrete proteins to induce an immune response, as well as to recruit other immune cells to the site of infection and tissue damage. In this study, we characterized the secretome (i.e., the global pattern of secreted proteins) of ATP-stimulated human macrophages. We show that ATP stimulation activates robust vesicle-mediated unconventional protein secretion, including exosome release and membrane shedding, from human macrophages...
September 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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