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https://www.readbyqxmd.com/read/28734869/p2x-receptors-up-regulate-the-cell-surface-expression-of-the-neuronal-glycine-transporter-glyt2
#1
Lucía Villarejo-López, Esperanza Jiménez, David Bartolomé-Martín, Francisco Zafra, Pablo Lapunzina, Carmen Aragón, Beatriz López-Corcuera
Glycinergic inhibitory neurons of the spinal dorsal horn exert critical control over the conduction of nociceptive signals to higher brain areas. The neuronal glycine transporter 2 (GlyT2) is involved in the recycling of synaptic glycine from the inhibitory synaptic cleft and its activity modulates intra and extracellular glycine concentrations. In this report we show that the stimulation of P2X purinergic receptors with βγ-methylene adenosine 5'-triphosphate induces the up-regulation of GlyT2 transport activity by increasing total and plasma membrane expression and reducing transporter ubiquitination...
July 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28734063/atp-and-astrocytes-play-a-prominent-role-in-the-control-of-the-respiratory-pattern-generator-in-the-lamprey
#2
Elenia Cinelli, Ludovica Iovino, Donatella Mutolo
The role of ATP and astrocytes in respiratory rhythm modulation has been recently investigated in neonatal rodents. However, no information on the role of ATP and astrocytes within the respiratory network of the lamprey is available, particularly within the paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator. To address these issues, the present study was carried out on isolated brainstems of the adult lamprey. Bath application of ATP caused marked increases in respiratory frequency followed by decreases in the respiratory motor output, mediated by the ATP metabolite adenosine at the level of the pTRG...
July 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28733972/expression-and-function-of-the-metabotropic-purinergic-p2y-receptor-family-in-experimental-seizure-models-and-patients-with-drug-refractory-epilepsy
#3
Mariana Alves, Rosa Gomez-Villafuertes, Norman Delanty, Michael A Farrell, Donncha F O'Brien, Maria Teresa Miras-Portugal, Miguel Diaz Hernandez, David C Henshall, Tobias Engel
OBJECTIVE: ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy...
July 21, 2017: Epilepsia
https://www.readbyqxmd.com/read/28728214/p2x-receptor-channels-in-chronic-pain-pathways
#4
REVIEW
Louis-Philippe Bernier, Ariel R Ase, Philippe Séguéla
Chronic pain is a highly prevalent debilitating condition for which treatment options remain limited for many patients. Ionotropic ATP signaling through excitatory and calcium-permeable P2X receptor-channels is now rightfully considered as a critical player in pathological pain generation and maintenance, therefore their selective targeting represents a therapeutic opportunity with promising yet untapped potential. Recent advances in the structural, functional and pharmacological characterization of rodent and human ATP-gated P2X receptor-channels have shed brighter light on the role of specific subtypes in the pathophysiology of chronic inflammatory, neuropathic or cancer pain...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28715108/ivermectin-activates-girk-channels-in-a-pip2-dependent-g%C3%AE-%C3%AE-independent-manner-and-an-amino-acid-residue-at-the-slide-helix-governs-the-activation
#5
I-Shan Chen, Michihiro Tateyama, Yuko Fukata, Motonari Uesugi, Yoshihiro Kubo
Ivermectin (IVM) is a widely used antiparasitic drug in humans and pets which activates glutamate-gated Cl(-) channel in parasites. It is also known that IVM binds to the transmembrane domains (TMs) of several ligand-gated channels, such as Cys-loop receptors and P2X receptors. In this study, we found that the G-protein-gated inwardly rectifying K(+) (GIRK) channel is activated by IVM directly. By electrophysiological recordings in Xenopus oocytes, we observed that IVM activates GIRK channel in a phosphatidylinositol-4,5-biphosphate (PIP2 )-dependent manner, and that the IVM-mediated GIRK activation is independent of Gβγ ...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28712872/suppression-of-cd36-attenuates-adipogenesis-with-a-reduction-of-p2x7-expression-in-3t3-l1-cells
#6
Huanqing Gao, Danyang Li, Ping Yang, Lei Zhao, Li Wei, Yaxi Chen, Xiong Z Ruan
Adipogenesis is a process of differentiation from preadipocyte into adipocyte, and is regulated by several transcription factors, including the peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT-enhancer-binding protein alpha (C/EBPα). CD36 is a membrane protein which contributes to the metabolic disorders such as obesity. Although the previous study demonstrated CD36 participated in the progression of adipogenesis, the mechanism is still unclear. We report here that knockdown of CD36 expression by CD36 small interfering RNA (siRNA) resulted in a reduction of adipocyte differentiation and adipogenic protein expression...
July 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28687781/p2x7-receptor-antagonism-modulates-il-1%C3%AE-and-mmp9-in-human-atherosclerotic-vessels
#7
Maria Lombardi, Maria Elena Mantione, Domenico Baccellieri, David Ferrara, Renata Castellano, Roberto Chiesa, Ottavio Alfieri, Chiara Foglieni
In atherosclerosis, matrix metallopeptidases (MMPs) contribute to plaque rupture through weakening of the fibrous cap. Pleiotropic P2X purinoceptor 7 (P2X7), expressed in the carotid plaque (PL), is involved in interleukin 1 beta (IL-1β) release that may influence MMP9 generation, thus their possible modulation through acting on P2X7 was investigated. P2X7-related machinery was characterized and the effects of P2X7 antagonists (A740003, KN62) and MMPs inhibitors (Batimastat, Ro28-2653) were studied in ex-vivo tissue cultures of human PL's vs...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28677119/atp-evokes-ca-2-signals-in-cultured-foetal-human-cortical-astrocytes-entirely-through-g-protein-coupled-p2y-receptors
#8
Margit S Muller, Colin W Taylor
Extracellular ATP plays important roles in coordinating the activities of astrocytes and neurons, and aberrant signalling is associated with neurodegenerative diseases. In rodents, ATP stimulates opening of Ca(2+) -permeable channels formed by P2X receptor subunits in the plasma membrane. It is widely assumed, but not verified, that P2X receptors also evoke Ca(2+) signals in human astrocytes. Here we directly assess this hypothesis. We showed that cultured foetal cortical human astrocytes express mRNA for several P2X receptor subunits (P2X4 , P2X5 , P2X6 ) and G-protein-coupled P2Y receptors (P2Y1 , P2Y2 , P2Y6 , P2Y11 )...
July 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28673711/activation-of-p2x3-receptors-in-the-cerebrospinal-fluid-contacting-nucleus-neurons-reduces-formalin-induced-pain-behavior-via-pag-in-a-rat-model
#9
Peng-Fei Liu, Hong-Zhi Fang, Yan Yang, Qing-Qing Zhang, Qiang-Qiang Zhou, Song-Song Chen, Fang Zhou, Li-Cai Zhang
The cerebrospinal fluid (CSF)-contacting nucleus is implicated in the descending inhibitory pathway in pain processing, whereas the cellular and molecular mechanisms underpinning CSF-contacting nucleus regulating pain signals remains largely elusive. ATP is evidenced to inhibit pain transmission at supraspinal level by the mediation of the receptor P2X, wherein its subtype P2X3 is identified as the most potent. Our present experiment investigated the functionality of P2X3 receptors in CSF-contacting nucleus in the formalin-evoked inflammatory pain...
June 30, 2017: Neuroscience
https://www.readbyqxmd.com/read/28671713/complement-c5a-induced-changes-in-neutrophil-morphology-during-inflammation
#10
Stephanie Denk, Ronald P Taylor, Rebecca Wiegner, Erika M Cook, Margaret A Lindorfer, Katharina Pfeiffer, Stephan Paschke, Tim Eiseler, Manfred Weiss, Eberhard Barth, John D Lambris, Miriam Kalbitz, Tobias Martin, Holger Barth, David A C Messerer, Florian Gebhard, Markus S Huber-Lang
The complement and neutrophil defense systems, as major components of innate immunity, are activated during inflammation and infection. For neutrophil migration to the inflamed region, we hypothesized that the complement activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure of human neutrophils to C5a, dose- and time-dependently resulted in a rapid C5a receptor-1 (C5aR1)-dependent shape-change, indicated by enhanced flow cytometric forward-scatter area values...
June 30, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28659591/alpha-lipoic-acid-suppresses-p2x-receptor-activities-and-visceral-hypersensitivity-to-colorectal-distention-in-diabetic-rats
#11
Ji Hu, Xin Qin, Zhen-Yuan Song, Pan-Pan Yang, Yu Feng, Qian Sun, Guang-Yin Xu, Hong-Hong Zhang
The present study was designed to investigate the roles of P2X3 receptors in dorsal root ganglion (DRG) neurons in colonic hypersensitivity and the effects of alpha-lipoic acid (ALA) on P2X3 receptor activity and colonic hypersensitivity of diabetic rats. Streptozotocin (STZ) was used to induce diabetic model. Abdominal withdrawal reflex (AWR) responding to colorectal distention (CRD) was recorded as colonic sensitivity. ATP-induced current density of colon-specific DRG (T13-L2 DRGs) neurons was measured with whole-cell patch clamp...
June 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28649232/ion-channels-of-pituitary-gonadotrophs-and-their-roles-in-signaling-and-secretion
#12
REVIEW
Stanko S Stojilkovic, Ivana Bjelobaba, Hana Zemkova
Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs) spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28648042/-effects-of-lappaconitine-on-pain-and-inflammatory-response-of-severely-burned-rats-and-the-mechanism
#13
C L Yang, Z R Wei, T H Zhang, X Q Zeng, B H Wu
Objective: To explore the effects of lappaconitine (LA) on pain and inflammatory response of severely burned rats and the mechanism. Methods: Forty SD rats were divided into healthy+ normal saline group, sham injury+ normal saline group, pure burn group, burn+ LA group, and healthy+ LA group according to the random number table (the same dividing method below), with 8 rats in each group. Rats in pure burn and burn+ LA groups were inflicted with about 32% total body surface area deep partial-thickness scald (hereinafter referred to as burn) on the back and right hind...
June 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28639248/p2x-receptor-activation
#14
Toshimitsu Kawate
Extracellular ATP-gated P2X receptors are trimeric non-selective cation channels important for many physiological events including immune response and neural transmission. These receptors belong to a unique class of ligand-gated ion channels composed of only six transmembrane helices and a relatively small extracellular domain that harbors three ATP-binding pockets. The crystal structures of P2X receptors, including the recent P2X3 structures representing three different stages of the gating cycle, have provided a compelling structural foundation for understanding how this class of ligand-gated ion channels function...
June 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28616989/reconstructed-serine-288-in-the-left-flipper-region-of-the-rat-p2x7-receptor-stabilizes-nonsensitized-states
#15
Yevheniia Ishchenko, Nataliia Novosolova, Kamil Khafizov, Geneviève 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 modeling approaches, we explored the role of the corresponding residue in the rat P2X7 receptor (rP2X7) by replacing the phenylalanine at position 288 with serine and characterizing the membrane currents generated by either the wild-type (WT) or the mutated rP2X7 receptor...
June 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28615626/neuronal-p2x7-receptor-induced-reactive-oxygen-species-production-contributes-to-nociceptive-behavior-in-mice
#16
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
#17
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
#18
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
#19
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
#20
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
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