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Purinergic Signalling

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https://www.readbyqxmd.com/read/28054206/the-effect-of-sinomenine-in-diabetic-neuropathic-pain-mediated-by-the-p2x3-receptor-in-dorsal-root-ganglia
#1
Shenqiang Rao, Shuangmei Liu, Lifang Zou, Tianyu Jia, Shanhong Zhao, Bing Wu, Zhihua Yi, Shouyu Wang, Yun Xue, Yun Gao, Changshui Xu, Guilin Li, Hong Xu, Chunping Zhang, Shangdong Liang
Type 2 diabetes mellitus (T2DM) accounts for more than 90% of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. Sinomenine is a natural bioactive component extracted from the Sinomenium acutum and has anti-inflammatory effects. The aim of our study was to investigate the effects of sinomenine on DNP mediated by the P2X3 receptor in dorsal root ganglia (DRG). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower than those of control rats...
January 4, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28028627/effect-of-electroacupuncture-on-the-cervicospinal-p2x7-receptor-fractalkine-cx3cr1-signaling-pathway-in-a-rat-neck-incision-pain-model
#2
Y H Gao, C W Li, J Y Wang, L H Tan, C L Duanmu, X H Jing, X R Chang, J L Liu
Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation...
December 27, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/28025718/conformational-changes-during-human-p2x7-receptor-activation-examined-by-structural-modelling-and-cysteine-based-cross-linking-studies
#3
Emily A Caseley, Stephen P Muench, Lin-Hua Jiang
The P2X7 receptor (P2X7R) is important in mediating a range of physiological functions and pathologies associated with tissue damage and inflammation and represents an attractive therapeutic target. However, in terms of their structure-function relationships, the mammalian P2X7Rs remain poorly characterised compared to some of their other P2XR counterparts. In this study, combining cysteine-based cross-linking and whole-cell patch-clamp recording, we examined six pairs of residues (A44/I331, D48/I331, I58/F311, S60/L320, I75/P177 and K81/V304) located in different parts of the extracellular and transmembrane domains of the human P2X7R...
December 26, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27966087/signaling-pathways-underlying-the-antidepressant-like-effect-of-inosine-in-mice
#4
Filipe Marques Gonçalves, Vivian Binder Neis, Débora Kurrle Rieger, Mark William Lopes, Isabella A Heinrich, Ana Paula Costa, Ana Lúcia S Rodrigues, Manuella P Kaster, Rodrigo Bainy Leal
Inosine is a purine nucleoside formed by the breakdown of adenosine that elicits an antidepressant-like effect in mice through activation of adenosine A1 and A2A receptors. However, the signaling pathways underlying this effect are largely unknown. To address this issue, the present study investigated the influence of extracellular-regulated protein kinase (ERK)1/2, Ca(2+)/calmoduline-dependent protein kinase (CaMKII), protein kinase A (PKA), phosphoinositide 3-kinase (PI3K)/Akt, and glycogen synthase kinase 3beta (GSK-3β) modulation in the antiimmobility effect of inosine in the tail suspension test (TST) in mice...
December 13, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27915383/a-covalent-antagonist-for-the-human-adenosine-a2a-receptor
#5
Xue Yang, Guo Dong, Thomas J M Michiels, Eelke B Lenselink, Laura Heitman, Julien Louvel, Ad P IJzerman
The structure of the human A2A adenosine receptor has been elucidated by X-ray crystallography with a high affinity non-xanthine antagonist, ZM241385, bound to it. This template molecule served as a starting point for the incorporation of reactive moieties that cause the ligand to covalently bind to the receptor. In particular, we incorporated a fluorosulfonyl moiety onto ZM241385, which yielded LUF7445 (4-((3-((7-amino-2-(furan-2-yl)-[1, 2, 4]triazolo[1,5-a][1, 3, 5]triazin-5-yl)amino)propyl)carbamoyl)benzene sulfonyl fluoride)...
December 3, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27900516/nucleotides-and-nucleoside-signaling-in-the-regulation-of-the-epithelium-to-mesenchymal-transition-emt
#6
REVIEW
A S Martínez-Ramírez, M Díaz-Muñoz, A Butanda-Ochoa, F G Vázquez-Cuevas
The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities...
November 29, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27866341/the-role-of-the-p2x7-receptor-in-murine-cutaneous-leishmaniasis-aspects-of-inflammation-and-parasite-control
#7
Vanessa Ribeiro Figliuolo, Suzana Passos Chaves, Luiz Eduardo Baggio Savio, Maria Luiza Prates Thorstenberg, Érika Machado Salles, Christina Maeda Takiya, Maria Regina D'Império-Lima, Herbert Leonel de Matos Guedes, Bartira Rossi-Bergmann, Robson Coutinho-Silva
Leishmania amazonensis is the etiological agent of diffuse cutaneous leishmaniasis. The immunopathology of leishmaniasis caused by L. amazonensis infection is dependent on the pathogenic role of effector CD4(+) T cells. Purinergic signalling has been implicated in resistance to infection by different intracellular parasites. In this study, we evaluated the role of the P2X7 receptor in modulating the immune response and susceptibility to infection by L. amazonensis. We found that P2X7-deficient mice are more susceptible to L...
November 19, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27858314/genetically-dissecting-p2rx7-expression-within-the-central-nervous-system-using-conditional-humanized-mice
#8
Michael W Metzger, Sandra M Walser, Fernando Aprile-Garcia, Nina Dedic, Alon Chen, Florian Holsboer, Eduardo Arzt, Wolfgang Wurst, Jan M Deussing
The purinergic P2X7 receptor (P2X7R) has attracted considerable interest as a potential target for various central nervous system (CNS) pathologies including affective and neurodegenerative disorders. To date, the distribution and cellular localization of the P2X7R in the brain are not fully resolved and a matter of debate mainly due to the limitations of existing tools. However, this knowledge should be a prerequisite for understanding the contribution of the P2X7R to brain disease. Here, we generated a genetic mouse model by humanizing the P2X7R in the mouse as mammalian model organism...
November 17, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27848070/diadenosine-tetraphosphate-as-a-potential-therapeutic-nucleotide-to-treat-glaucoma
#9
Begoña Fonseca, Alejandro Martínez-Águila, María J Pérez de Lara, Jesús Pintor
Glaucoma is a neurodegenerative disease that produces blindness. The main factor associated with this disease is an abnormally elevated intraocular pressure (IOP). To date, some attempts have been made to demonstrate the role of nucleotides modulating IOP, but never in a model of glaucoma. The DBA/2J mouse is an animal that develops the pathology spontaneously, starting from the typical rise in IOP at 9 months of age. Using this animal model, together with a control mouse, C57BL/6J, it has been possible to monitor the elevation in IOP in the glaucomatous mice and to check the ability of the dinucleotide diadenosine tetraphosphate AKA Ap4A to reduce IOP...
November 16, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27848069/adenosine-receptors-regulatory-players-in-the-preservation-of-mitochondrial-function-induced-by-ischemic-preconditioning-of-rat-liver
#10
Filipe V Duarte, João A Amorim, Ana T Varela, João S Teodoro, Ana P Gomes, Rodrigo A Cunha, Carlos M Palmeira, Anabela P Rolo
Although adenosine A1 receptors (A1R) have been associated to ischemic preconditioning (IPC), direct evidence for their ability to preserve mitochondrial function upon hepatic preconditioning is still missing and could represent a novel strategy to boost the quality of liver transplants. We tested if the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) prevented IPC in the liver and if the A1R agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) might afford a pharmacological preconditioning. Livers underwent a 120 min of 70% warm ischemia and 16 h of reperfusion (I/R), and the IPC group underwent a 5-min ischemic episode followed by a 10-min period of reperfusion before I/R...
November 15, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27832456/regulation-of-cd73-in-the-development-of-lower-limb-atherosclerosis
#11
Juho Jalkanen, Maija Hollmén, Sirpa Jalkanen, Harri Hakovirta
Atherosclerosis is an inflammatory process of the arterial wall. CD73 (also known as ecto-5'-nucleotidase) is a key regulator of cell signaling in response to inflammation and hypoxia, and may be important in the development of atherosclerosis. Recently, we have shown that high CD73 activity can be detected in the serum of patients with peripheral arterial disease (PAD). Using this same PAD patient cohort of 226 subjects with 38 femoral artery samples obtained during surgical endarcterectomy and control artery samples taken during autopsy, we explored the association of serum CD73 activity with overall atherosclerotic burden and the expression of CD73 in mature and developing plaques...
November 10, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27817132/inhibitory-effect-of-estrogen-receptor-beta-on-p2x3-receptors-during-inflammation-in-rats
#12
Qian Jiang, Wen-Xin Li, Jia-Run Sun, Tian-Tian Zhu, Juan Fan, Li-Hua Yu, Geoffrey Burnstock, Hua Yang, Bei Ma
Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041...
November 5, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27815804/lung-injury-during-lps-induced-inflammation-occurs-independently-of-the-receptor-p2y1
#13
Elisabetta Liverani
Disruption of the lung endothelial and epithelial barriers during acute inflammation leads to excessive neutrophil migration. It is likely that activated platelets promote pulmonary recruitment of neutrophils during inflammation, and previous studies have found that anti-platelet therapy and depletion of circulating platelets have lung-protective effects in different models of inflammation. Because ADP signaling is important for platelet activation, I investigated the role of the ADP-receptor P2Y1, a G protein-coupled receptor expressed on the surface of circulating platelets, during lipopolysaccharide (LPS)-induced inflammation and lung injury in P2Y1-null and wild-type mice...
November 4, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27826687/erratum-to-lack-of-functional-p2x7-receptor-aggravates-brain-edema-development-after-middle-cerebral-artery-occlusion
#14
Melanie Kaiser, Anja Penk, Heike Franke, Ute Krügel, Wolfgang Nörenberg, Daniel Huster, Michael Schaefer
No abstract text is available yet for this article.
December 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27650530/adenosine-a2a-receptor-and-ecto-5-nucleotidase-cd73-are-upregulated-in-hippocampal-astrocytes-of-human-patients-with-mesial-temporal-lobe-epilepsy-mtle
#15
Aurora R Barros-Barbosa, Fátima Ferreirinha, Ângela Oliveira, Marina Mendes, M Graça Lobo, Agostinho Santos, Rui Rangel, Julie Pelletier, Jean Sévigny, J Miguel Cordeiro, Paulo Correia-de-Sá
Refractoriness to existing medications of up to 80 % of the patients with mesial temporal lobe epilepsy (MTLE) prompts for finding new antiepileptic drug targets. The adenosine A2A receptor emerges as an interesting pharmacological target since its excitatory nature partially counteracts the dominant antiepileptic role of endogenous adenosine acting via inhibitory A1 receptors. Gain of function of the excitatory A2A receptor has been implicated in a significant number of brain pathologies commonly characterized by neuronal excitotoxicity...
December 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27613537/guanosine-prevents-nitroxidative-stress-and-recovers-mitochondrial-membrane-potential-disruption-in-hippocampal-slices-subjected-to-oxygen-glucose-deprivation
#16
Daniel T Thomaz, Tharine A Dal-Cim, Wagner C Martins, Maurício Peña Cunha, Débora Lanznaster, Andreza F de Bem, Carla I Tasca
Guanosine, the endogenous guanine nucleoside, prevents cellular death induced by ischemic events and is a promising neuroprotective agent. During an ischemic event, nitric oxide has been reported to either cause or prevent cell death. Our aim was to evaluate the neuroprotective effects of guanosine against oxidative damage in hippocampal slices subjected to an in vitro ischemia model, the oxygen/glucose deprivation (OGD) protocol. We also assessed the participation of nitric oxide synthase (NOS) enzymes activity on the neuroprotection promoted by guanosine...
December 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27585449/anti-aging-effects-of-guanosine-in-glial-cells
#17
Débora Guerini Souza, Bruna Bellaver, Larissa Daniele Bobermin, Diogo Onofre Souza, André Quincozes-Santos
Guanosine, a guanine-based purine, has been shown to exert beneficial roles in in vitro and in vivo injury models of neural cells. Guanosine is released from astrocytes and modulates important astroglial functions, including glutamatergic metabolism, antioxidant, and anti-inflammatory activities. Astrocytes are crucial for regulating the neurotransmitter system and synaptic information processes, ionic homeostasis, energy metabolism, antioxidant defenses, and the inflammatory response. Aging is a natural process that induces numerous changes in the astrocyte functionality...
December 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27577957/adenosine-arrests-breast-cancer-cell-motility-by-a3-receptor-stimulation
#18
Carola Ledderose, Marco M Hefti, Yu Chen, Yi Bao, Thomas Seier, Linglin Li, Tobias Woehrle, Jingping Zhang, Wolfgang G Junger
In neutrophils, adenosine triphosphate (ATP) release and autocrine purinergic signaling regulate coordinated cell motility during chemotaxis. Here, we studied whether similar mechanisms regulate the motility of breast cancer cells. While neutrophils and benign human mammary epithelial cells (HMEC) form a single leading edge, MDA-MB-231 breast cancer cells possess multiple leading edges enriched with A3 adenosine receptors. Compared to HMEC, MDA-MB-231 cells overexpress the ectonucleotidases ENPP1 and CD73, which convert extracellular ATP released by the cells to adenosine that stimulates A3 receptors and promotes cell migration with frequent directional changes...
December 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27565966/cd39-overexpression-does-not-attenuate-renal-fibrosis-in-the-unilateral-ureteric-obstructive-model-of-chronic-kidney-disease
#19
Veena Roberts, B Lu, J Chia, P J Cowan, K M Dwyer
Chronic kidney disease has multiple etiologies, but its single, hallmark lesion is renal fibrosis. CD39 is a key purinergic enzyme in the hydrolysis of ATP and increased CD39 activity on regulatory T cells (Treg) is protective in adriamycin-induced renal fibrosis. We examined the effect of overexpression of human CD39 on the development of renal fibrosis in the unilateral ureteric obstructive (UUO) model, a model widely used to study the molecular and cellular factors involved in renal fibrosis. Mice overexpressing human CD39 (CD39Tg) and their wild-type (WT) littermates were subjected to UUO; renal histology and messenger RNA (mRNA) levels of adenosine receptors and markers of renal fibrosis were examined up to 14 days after UUO...
December 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27565965/p2y2r-is-a-direct-target-of-hif-1%C3%AE-and-mediates-secretion-dependent-cyst-growth-of-renal-cyst-forming-epithelial-cells
#20
Andre Kraus, Steffen Grampp, Margarete Goppelt-Struebe, Rainer Schreiber, Karl Kunzelmann, Dorien J M Peters, Jens Leipziger, Gunnar Schley, Johannes Schödel, Kai-Uwe Eckardt, Bjoern Buchholz
Polycystic kidney diseases are characterized by numerous renal cysts that continuously enlarge resulting in compression of intact nephrons and tissue hypoxia. Recently, we have shown that hypoxia-inducible factor (HIF)-1α promotes secretion-dependent cyst expansion, presumably by transcriptional regulation of proteins that are involved in calcium-activated chloride secretion. Here, we report that HIF-1α directly activates expression of the purinergic receptor P2Y2R in human primary renal tubular cells. In addition, we found that P2Y2R is highly expressed in cyst-lining cells of human ADPKD kidneys as well as PKD1 orthologous mouse kidneys...
December 2016: Purinergic Signalling
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