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https://www.readbyqxmd.com/read/28332633/structural-insights-into-the-nucleotide-base-specificity-of-p2x-receptors
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
February 24, 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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28165191/efficient-catalysis-of-hydrogen-evolution-reaction-from-ws2-1-x-p2x-nanoribbons
#13
Tofik Ahmed Shifa, Fengmei Wang, Kaili Liu, Zhongzhou Cheng, Kai Xu, Zhenxing Wang, Xueying Zhan, Chao Jiang, Jun He
The rational design of Earth abundant electrocatalysts for efficiently catalyzing hydrogen evolution reaction (HER) is believed to lead to the generation of carbon neutral energy carrier. Owing to their fascinating chemical and physical properties, transition metal dichalcogenides (TMDs) are widely studied for this purpose. Of particular note is that doping by foreign atom can bring the advent of electronic perturbation, which affects the intrinsic catalytic property. Hence, through doping, the catalytic activity of such materials could be boosted...
February 6, 2017: Small
https://www.readbyqxmd.com/read/28163685/ionotropic-p2x-atp-receptor-channels-mediate-purinergic-signaling-in-mouse-odontoblasts
#14
Yuta Shiozaki, Masaki Sato, Maki Kimura, Toru Sato, Masakazu Tazaki, Yoshiyuki Shibukawa
ATP modulates various functions in the dental pulp cells, such as intercellular communication and neurotransmission between odontoblasts and neurons, proliferation of dental pulp cells, and odontoblast differentiation. However, functional expression patterns and their biophysical properties of ionotropic ATP (P2X) receptors (P2X1-P2X7) in odontoblasts were still unclear. We examined these properties of P2X receptors in mouse odontoblasts by patch-clamp recordings. K(+)-ATP, nonselective P2X receptor agonist, induced inward currents in odontoblasts in a concentration-dependent manner...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28093236/extracellular-atp-and-adenosine-the-yin-and-yang-in-immune-responses
#15
REVIEW
M M Faas, T Sáez, P de Vos
Extracellular adenosine 5'-triphosphate (ATP) and adenosine molecules are intimately involved in immune responses. ATP is mostly a pro-inflammatory molecule and is released during hypoxic condition and by necrotic cells, as well as by activated immune cells and endothelial cells. However, under certain conditions, for instance at low concentrations or at prolonged exposure, ATP may also have anti-inflammatory properties. Extracellular ATP can activate both P2X and P2Y purinergic receptors. Extracellular ATP can be hydrolyzed into adenosine in a two-step enzymatic process involving the ectonucleotidases CD39 (ecto-apyrase) and CD73...
January 16, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28011630/a-polycystin-type-transient-receptor-potential-trp-channel-that-is-activated-by-atp
#16
David Traynor, Robert R Kay
ATP and ADP are ancient extra-cellular signalling molecules that in Dictyostelium amoebae cause rapid, transient increases in cytosolic calcium due to an influx through the plasma membrane. This response is independent of hetero-trimeric G-proteins, the putative IP3 receptor IplA and all P2X channels. We show, unexpectedly, that it is abolished in mutants of the polycystin-type transient receptor potential channel, TrpP. Responses to the chemoattractants cyclic-AMP and folic acid are unaffected in TrpP mutants...
February 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28004778/glycosides-from-edible-sea-cucumbers-stimulate-macrophages-via-purinergic-receptors
#17
Dmitry Aminin, Evgeny Pislyagin, Maxim Astashev, Andrey Es'kov, Valery Kozhemyako, Sergei Avilov, Elena Zelepuga, Ekaterina Yurchenko, Leonid Kaluzhskiy, Emma Kozlovskaya, Alexis Ivanov, Valentin Stonik
Since ancient times, edible sea cucumbers have been considered a jewel of the seabed and used in Asian folk medicine for stimulation of resistance against different diseases. However, the power of this sea food has not been established on a molecular level. A particular group of triterpene glycosides was found to be characteristic metabolites of the animals, responsible for this biological action. Using one of them, cucumarioside A2-2 (CA2-2) from the edible Cucumaria japonica species as an example as well as inhibitory analysis, patch-clamp on single macrophages, small interfering RNA technique, immunoblotting, SPR analysis, computer modeling and other methods, we demonstrate low doses of CA2-2 specifically to interact with P2X receptors (predominantly P2X4) on membranes of mature macrophages, enhancing the reversible ATP-dependent Ca(2+) intake and recovering Ca(2+) transport at inactivation of these receptors...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#18
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
#19
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
#20
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
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