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https://www.readbyqxmd.com/read/29729039/effects-of-calcium-and-sodium-on-atp-induced-vasopressin-release-from-rat-isolated-neurohypophysial-terminals
#1
E E Custer, T K Knott, S Ortiz-Miranda, J R Lemos
ATP-receptors (P2X2, P2X3, P2X4 & P2X7) are found in neurohypophysial terminals (NHT). These purinergic receptor subtypes are known to be cation selective. Here we confirm that both sodium (Na+ ) and calcium (Ca2+ ) are permeable through these NHT purinergic receptors, but to varying degrees (91% vs. 9%, respectively). Furthermore, extracellular calcium inhibits the ATP-current magnitude. Thus, the objective of this study was to determine the effects of extracellular Na+ vs. Ca2+ on ATP-induced vasopressin (AVP) release from populations of rat isolated NHT...
May 4, 2018: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29723484/investigational-drugs-for-alcohol-use-disorders-a-review-of-preclinical-data
#2
Sarah S Ch'ng, Andrew J Lawrence
Alcohol use disorders (AUDs) are one of the leading causes of preventable death in the developed world. In the U.S., only three FDA-approved pharmacotherapies for AUDs currently exist, but at a population level they display poor efficacy, low compliance rates, and adverse side effects. Therefore, identifying novel neurobiological targets for pharmacological treatment of AUDs is of urgent concern. Areas covered: We discuss recent preclinical data on investigational drugs that have been assessed for their therapeutic potential in AUDs...
May 3, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29652806/excessive-extracellular-atp-desensitizes-p2y2-and-p2x4-atp-receptors-provoking-surfactant-impairment-ending-in-ventilation-induced-lung-injury
#3
REVIEW
Djo Hasan, Joshua Satalin, Philip van der Zee, Michaela Kollisch-Singule, Paul Blankman, Atsuko Shono, Peter Somhorst, Corstiaan den Uil, Han Meeder, Toru Kotani, Gary F Nieman
Stretching the alveolar epithelial type I (AT I) cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP) (purinergic signaling). Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases...
April 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29604959/coupling-of-p2y-receptors-to-ca-2-mobilization-in-mesenchymal-stromal-cells-from-the-human-adipose-tissue
#4
Polina D Kotova, Marina F Bystrova, Olga A Rogachevskaja, Alexander A Khokhlov, Veronika Yu Sysoeva, Vsevolod A Tkachuk, Stanislav S Kolesnikov
The purinergic transduction was examined in mesenchymal stromal cells (MSCs) from the human adipose tissue, and several nucleotides, including ATP, UTP, and ADP, were found to mobilize cytosolic Ca2+ . Transcripts for multiple purinoreceptors were detected in MSC preparations, including A1 , A2A , A2B , P2Y1 , P2Y2 , P2Y4 , P2Y6 , P2Y11 , P2Y13 , P2Y14 , P2X2 , P2X4 , and P2X7 . Cellular responses to nucleotides were insignificantly sensitive to bath Ca2+ , pointing at a minor contribution of Ca2+ entry, and were suppressed by U73122 and 2-APB, implicating the phosphoinositide cascade in coupling P2Y receptors to Ca2+ release...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29541027/p2y-6-receptors-regulate-cxcl10-expression-and-secretion-in-mouse-intestinal-epithelial-cells
#5
Mabrouka Salem, Alain Tremblay, Julie Pelletier, Bernard Robaye, Jean Sévigny
In this study, we investigated the role of extracellular nucleotides in chemokine (KC, MIP-2, MCP-1, and CXCL10) expression and secretion by murine primary intestinal epithelial cells (IECs) with a focus on P2Y6 receptors. qRT-PCR experiments showed that P2Y6 was the dominant nucleotide receptor expressed in mouse IEC. In addition, the P2Y6 ligand UDP induced expression and secretion of CXCL10. For the other studies, we took advantage of mice deficient in P2Y6 ( P2ry6 -/- ). Similar expression levels of P2Y1 , P2Y2 , P2X2, P2X4, and A2A were detected in P2ry6 -/- and WT IEC...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29512852/purinergic-receptor-types-in-the-hypothalamic-neurohypophysial-system
#6
REVIEW
José R Lemos, Edward E Custer, Sonia Ortiz-Miranda
Many different types of purinergic receptors are present in the Hypothalamic-Neurohypophysial System (HNS), which synthesizes and releases vasopressin and oxytocin. The specific location of purinergic receptor subtypes has important functional repercussions for neuronal activity and synaptic output. Yet, until the advent of receptor KOs, this had been hindered by the low selectivity of the available pharmacological tools. The HNS offers an excellent opportunity to differentiate the functional properties of these purinergic receptors in cell bodies vs...
March 7, 2018: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29500584/preclinical-evaluation-of-avermectins-as-novel-therapeutic-agents-for-alcohol-use-disorders
#7
REVIEW
Sheraz Khoja, Nhat Huynh, Alicia M P Warnecke, Liana Asatryan, Michael W Jakowec, Daryl L Davies
The deleterious effects of alcohol use disorders (AUDs) on human health have been documented worldwide. The enormous socioeconomic burden coupled with lack of efficacious pharmacotherapies underlies the need for improved treatment strategies. At present, there is a growing body of preclinical evidence that demonstrates the potential of avermectins [ivermectin (IVM), selamectin (SEL), abamectin (ABM), and moxidectin (MOX)] in treatment of AUDs. Avermectins are derived by fermentation of soil micro-organism, Streptomyces avermitilis, and have been extensively used for treatment of parasitic infections...
June 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29477921/reduced-expression-of-purinergic-p2x4-receptors-increases-voluntary-ethanol-intake-in-c57bl-6j-mice
#8
Sheraz Khoja, Nhat Huynh, Liana Asatryan, Michael W Jakowec, Daryl L Davies
Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ionotropic receptors that are gated by adenosine 5'-triphosphate (ATP). Accumulating evidence indicates that P2X4Rs play an important role in regulation of ethanol intake. At the molecular level, ethanol's inhibitory effects on P2X4Rs are antagonized by ivermectin (IVM), in part, via action on P2X4Rs. Behaviorally, male mice deficient in the p2rx4 gene (P2X4R knockout [KO]) have been shown to exhibit a transient increase in ethanol intake over a period of 4 days, as demonstrated by social and binge drinking paradigms...
May 2018: Alcohol
https://www.readbyqxmd.com/read/29457680/chronic-lead-exposure-enhances-the-sympathoexcitatory-response-associated-with-p2x4-receptor-in-rat-stellate-ganglia
#9
Gaochun Zhu, Zhenying Chen, Bo Dai, Chaoran Zheng, Huaide Jiang, Yurong Xu, Xuan Sheng, Jingjing Guo, Yu Dan, Shangdong Liang, Guilin Li
Chronic lead exposure causes peripheral sympathetic nerve stimulation, including increased blood pressure and heart rate. Purinergic receptors are involved in the sympathoexcitatory response induced by myocardial ischemia injury. However, whether P2X4 receptor participates in sympathoexcitatory response induced by chronic lead exposure and the possible mechanisms are still unknown. The aim of this study was to explore the change of the sympathoexcitatory response induced by chronic lead exposure via the P2X4 receptor in the stellate ganglion (SG)...
February 19, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29456508/the-molecular-determinants-of-small-molecule-ligand-binding-at-p2x-receptors
#10
Gaia Pasqualetto, Andrea Brancale, Mark T Young
P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP-their physiological ligand-is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo - state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homology modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29431813/a-gold-nano-electrode-for-single-ion-channel-recordings
#11
Daichi Okuno, Minako Hirano, Hiroaki Yokota, Junya Ichinose, Takamitsu Kira, Taiki Hijiya, Chihiro Uozumi, Masahiro Yamakami, Toru Ide
The artificial bilayer single channel recording technique is commonly used to observe the detailed physiological properties of various ion channel proteins. It permits easy control of the solution and membrane lipid composition, and is also compatible with pharmacological screening devices. However, its use is limited due to low measurement efficiency. Here, we developed a novel artificial bilayer single channel recording technique in which solubilized ion channel proteins immobilized on a gold nano-electrode are directly incorporated into a lipid bilayer at the same time as the bilayer is formed at the tip of it on coming in contact with an aqueous-oil interface...
February 22, 2018: Nanoscale
https://www.readbyqxmd.com/read/29382907/role-of-p2x-4-receptor-in-mouse-voiding-function
#12
Weiqun Yu, Warren G Hill, Simon C Robson, Mark L Zeidel
Purinergic signalling plays an important role in the regulation of bladder smooth muscle (BSM) contractility, and P2X4 receptor is expressed in the bladder wall, where it may act by forming heteromeric receptors with P2X1 , the major purinergic force-generating muscle receptor. To test this hypothesis, we examined mouse BSM contractile properties in the absence and presence of selective P2X1 (NF449 & NF279) and P2X4 antagonists (5-BDBD). These drugs inhibited BSM purinergic contraction only partially, suggesting the possibility of a heteromeric receptor...
January 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29358186/a-role-for-p2x-4-receptors-in-lysosome-function
#13
REVIEW
Ruth D Murrell-Lagnado
No abstract text is available yet for this article.
February 5, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29336303/keratinocytes-mediate-innocuous-and-noxious-touch-via-atp-p2x4-signaling
#14
Francie Moehring, Ashley M Cowie, Anthony D Menzel, Andy D Weyer, Michael Grzybowski, Thiago Arzua, Aron M Geurts, Oleg Palygin, Cheryl L Stucky
The first point of our body's contact with tactile stimuli (innocuous and noxious) is the epidermis, the outermost layer of skin that is largely composed of keratinocytes. Here, we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo. We show that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated by complementary cutaneous ATP release and degradation experiments...
January 16, 2018: ELife
https://www.readbyqxmd.com/read/29282210/atp-is-stored-in-lamellar-bodies-to-activate-vesicular-p2x-4-in-an-autocrine-fashion-upon-exocytosis
#15
Giorgio Fois, Veronika Eva Winkelmann, Lara Bareis, Laura Staudenmaier, Elena Hecht, Charlotte Ziller, Konstantin Ehinger, Jürgen Schymeinsky, Christine Kranz, Manfred Frick
Vesicular P2X4 receptors are known to facilitate secretion and activation of pulmonary surfactant in the alveoli of the lungs. P2X4 receptors are expressed in the membrane of lamellar bodies (LBs), large secretory lysosomes that store lung surfactant in alveolar type II epithelial cells, and become inserted into the plasma membrane after exocytosis. Subsequent activation of P2X4 receptors by adenosine triphosphate (ATP) results in local fusion-activated cation entry (FACE), facilitating fusion pore dilation, surfactant secretion, and surfactant activation...
February 5, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29213241/interaction-of-purinergic-p2x4-and-p2x7-receptor-subunits
#16
Markus Schneider, Kirsten Prudic, Anja Pippel, Manuela Klapperstück, Ursula Braam, Christa E Müller, Günther Schmalzing, Fritz Markwardt
P2X4 and P2X7 are members of the P2X receptor family, comprising seven isoforms (P2X1-P2X7) that form homo- and heterotrimeric non-specific cation channels gated by extracellular ATP. P2X4 and P2X7 are widely coexpressed, particularly in secretory epithelial cells and immune and inflammatory cells, and regulate inflammation and nociception. Although functional heteromerization has been established for P2X2 and P2X3 subunits expressed in sensory neurons, there are contradictory reports regarding a functional interaction between P2X4 and P2X7 subunits...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29199560/lion-s-mane-medicinal-mushroom-hericium-erinaceus-agaricomycetes-modulates-purinoceptor-coupled-calcium-signaling-and-murine-nociceptive-behavior
#17
Pei-Shan Liu, Sheau-Huei Chueh, Chin-Chu Chen, Li-Ya Lee, Li-Yen Shiu
Hericium erinaceus is well known for the neurotrophic effect it confers by promoting nerve growth factor biosynthesis. We discovered a novel bioactivity of H. erinaceus in its ability to suppress adenosine triphosphate (ATP)-induced calcium signaling in neuronal PC12 cells. ATP, known primarily as a neurotransmitter, also acts on purinoceptors (P2 purinergic receptor [P2R]) to generate the cellular calcium signaling and secretion that mediate P2R physiological manifestations, including pain. Chronic pain reduces quality of life...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/29179879/p2x4-a-fast-and-sensitive-purinergic-receptor
#18
REVIEW
Jaanus Suurväli, Pierre Boudinot, Jean Kanellopoulos, Sirje Rüütel Boudinot
Extracellular nucleotides have been recognized as important mediators of activation, triggering multiple responses via plasma membrane receptors known as P2 receptors. P2 receptors comprise P2X ionotropic receptors and G protein-coupled P2Y receptors. P2X receptors are expressed in many tissues, where they are involved in a number of functions including synaptic transmission, muscle contraction, platelet aggregation, inflammation, macrophage activation, differentiation and proliferation, neuropathic and inflammatory pain...
October 2017: Biomedical Journal
https://www.readbyqxmd.com/read/29077063/p2x4-receptor-dependent-ca-2-influx-in-model-human-monocytes-and-macrophages
#19
Janice A Layhadi, Samuel J Fountain
Monocytes and macrophages express a repertoire of cell surface P2 receptors for adenosine 5'-triphosphate (ATP) a damage-associated molecular pattern molecule (DAMP), which are capable of raising cytoplasmic calcium when activated. This is achieved either through direct permeation (ionotropic P2X receptors) or by mobilizing intracellular calcium stores (metabotropic P2Y receptors). Here, a side-by-side comparison to investigate the contribution of P2X4 receptor activation in ATP-evoked calcium responses in model human monocytes and macrophages was performed...
October 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29063617/ivermectin-and-its-target-molecules-shared-and-unique-modulation-mechanisms-of-ion-channels-and-receptors-by-ivermectin
#20
I-Shan Chen, Yoshihiro Kubo
Ivermectin (IVM) is an antiparasitic drug that is used worldwide and rescues hundreds of millions of people from onchocerciasis and lymphatic filariasis. It was discovered by Satoshi Ōmura and William C. Campbell, to whom the 2015 Nobel Prize in Physiology or Medicine was awarded. It kills parasites by activating glutamate-gated Cl(-) channels, and it also targets several ligand-gated ion channels and receptors, including Cys-loop receptors, P2X4 receptors and fernesoid X receptors. Recently, we found that IVM also activates a novel target, the G-protein-gated inwardly rectifying K(+) channel, and also identified the structural determinant for the activation...
October 23, 2017: Journal of Physiology
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