keyword
MENU ▼
Read by QxMD icon Read
search

Purinergic

keyword
https://www.readbyqxmd.com/read/28735873/the-therapeutic-potential-of-purinergic-signalling
#1
REVIEW
Geoffrey Burnstock
This review is focused on the pathophysiology and therapeutic potential of purinergic signalling. A wide range of diseases are considered, including those of the central nervous system, skin, kidney, musculoskeletal, liver gut, lower urinary tract, cardiovascular, airways and reproductive systems, the special senses, infection, diabetes and obesity. Several purinergic drugs are already on the market, including P2Y12 receptor antagonists for stroke and thrombosis, P2Y2 receptor agonists for dry eye, A1 receptor agonists for supraventricular tachycardia...
July 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28734869/p2x-receptors-up-regulate-the-cell-surface-expression-of-the-neuronal-glycine-transporter-glyt2
#2
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/28734079/post-translational-palmitoylation-controls-the-voltage-gating-and-lipid-raft-association-of-calhm1-channel
#3
Akiyuki Taruno, Hongxin Sun, Koichi Nakajo, Tatsuro Murakami, Yasuyoshi Ohsaki, Mizuho A Kido, Fumihito Ono, Yoshinori Marunaka
Emerging roles of CALHM1, a recently discovered voltage-gated ion channel, include purinergic neurotransmission of tastes in taste buds and memory formation in the brain, highlighting its physiological importance. However, the regulatory mechanisms of the CALHM1 channel remain entirely unexplored, hindering full understanding of its contribution in vivo. In fact, the different gating properties of CALHM1 in vivo and in vitro suggest undiscovered regulatory mechanisms. Here, in searching for post-translational regulatory mechanisms, we discovered the regulation of CALHM1 gating and association with lipid microdomains via protein S-palmitoylation, the only reversible lipid modification of proteins on cysteine residues...
July 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28734063/atp-and-astrocytes-play-a-prominent-role-in-the-control-of-the-respiratory-pattern-generator-in-the-lamprey
#4
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
#5
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/28729619/effects-of-4-1h-quinolinone-derivative-a-novel-non-nucleotide-allosteric-purinergic-p2y-2-agonist-on-cardiomyocytes-in-neonatal-rats
#6
Kensuke Sakuma, Hideyuki Nakagawa, Tatsuo Oikawa, Masakuni Noda, Shota Ikeda
Purinergic P2Y 2 receptors, G-protein coupled receptors that primarily couple with Gαq/11-proteins, are activated equipotently by adenosine-5'-triphosphate (ATP) and uridine-5'-triphosphate. Evidence suggests that P2Y 2 agonists make potential drug candidates for the treatment of cardiovascular diseases. However, selective non-nucleotide, small-molecule P2Y 2 agonists have yet to be developed. In this report, we discuss Compound 89, a novel non-nucleotide allosteric P2Y 2 agonist that was active in signal transduction and gene induction, and in our in vitro cardiac hypertrophy model...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729424/molecular-determinants-of-acidic-ph-dependent-transport-of-human-equilibrative-nucleoside-transporter-3
#7
Md Fazlur Rahman, Candice Askwith, Rajgopal Govindarajan
Equilibrative nucleoside transporters (ENTs) translocate hydrophilic nucleosides across cellular membranes and are essential for salvage nucleotide synthesis and purinergic signaling. Unlike the prototypic human ENT members hENT1 and hENT2, which mediate plasma membrane nucleoside transport at pH 7.4, hENT3 is an acidic pH-activated lysosomal transporter partially localized to mitochondria. Recent studies demonstrate that hENT3 is indispensable for lysosomal homeostasis, and that mutations in hENT3 can result in a spectrum of lysosomal storage-like disorders...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28722654/a-lectin-receptor-kinase-as-a-potential-sensor-for-extracellular-nicotinamide-adenine-dinucleotide-in-arabidopsis-thaliana
#8
Chenggang Wang, Mingqi Zhou, Xudong Zhang, Jin Yao, Yanping Zhang, Zhonglin Mou
Nicotinamide adenine dinucleotide (NAD(+)) participates in intracellular and extracellular signaling events unrelated to metabolism. In animals, purinergic receptors are required for extracellular NAD(+) (eNAD(+)) to evoke biological responses, indicating that eNAD(+) may be sensed by cell-surface receptors. However, the identity of eNAD(+)-binding receptors still remains elusive. Here, we identify a lectin receptor kinase (LecRK), LecRK-I.8, as a potential eNAD(+) receptor in Arabidopsis. The extracellular lectin domain of LecRK-I...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28722539/an-autophagy-driven-pathway-of-atp-secretion-supports-the-aggressive-phenotype-of-braf-v600e-inhibitor-resistant-metastatic-melanoma-cells
#9
Shaun Martin, Aleksandra M Dudek-Peric, Abhishek D Garg, Heleen Roose, Seyma Demirsoy, Sofie Van Eygen, Freya Mertens, Peter Vangheluwe, Hugo Vankelecom, Patrizia Agostinis
The ingrained capacity of melanoma cells to rapidly evolve towards an aggressive phenotype is manifested by their increased ability to develop drug-resistance, evident in the case of vemurafenib, a therapeutic-agent targeting BRAF(V600E). Previous studies indicated a tight correlation between heightened melanoma-associated macroautophagy/autophagy and acquired Vemurafenib resistance. However, how this vesicular trafficking pathway supports Vemurafenib resistance remains unclear. Here, using isogenic human and murine melanoma cell lines of Vemurafenib-resistant and patient-derived melanoma cells with primary resistance to the BRAF(V600E) inhibitor, we found that the enhanced migration and invasion of the resistant melanoma cells correlated with an enhanced autophagic capacity and autophagosome-mediated secretion of ATP...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28720702/identification-of-a-vesicular-atp-release-inhibitor-for-the-treatment-of-neuropathic-and-inflammatory-pain
#10
Yuri Kato, Miki Hiasa, Reiko Ichikawa, Nao Hasuzawa, Atsushi Kadowaki, Ken Iwatsuki, Kazuhiro Shima, Yasuo Endo, Yoshiro Kitahara, Tsuyoshi Inoue, Masatoshi Nomura, Hiroshi Omote, Yoshinori Moriyama, Takaaki Miyaji
Despite the high incidence of neuropathic and inflammatory pain worldwide, effective drugs with few side effects are currently unavailable for the treatment of chronic pain. Recently, researchers have proposed that inhibitors of purinergic chemical transmission, which plays a key role in the pathological pain response, may allow for targeted treatment of pathological neuropathic and inflammatory pain. However, such therapeutic analgesic agents have yet to be developed. In the present study, we demonstrated that clodronate, a first-generation bisphosphonate with comparatively fewer side effects than traditional treatments, significantly attenuates neuropathic and inflammatory pain unrelated to bone abnormalities via inhibition of vesicular nucleotide transporter (VNUT), a key molecule for the initiation of purinergic chemical transmission...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28712872/suppression-of-cd36-attenuates-adipogenesis-with-a-reduction-of-p2x7-expression-in-3t3-l1-cells
#11
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/28712806/structures-of-human-a1-and-a2a-adenosine-receptors-with-xanthines-reveal-determinants-of-selectivity
#12
Robert K Y Cheng, Elena Segala, Nathan Robertson, Francesca Deflorian, Andrew S Doré, James C Errey, Cédric Fiez-Vandal, Fiona H Marshall, Robert M Cooke
The adenosine A1 and A2A receptors belong to the purinergic family of G protein-coupled receptors, and regulate diverse functions of the cardiovascular, respiratory, renal, inflammation, and CNS. Xanthines such as caffeine and theophylline are weak, non-selective antagonists of adenosine receptors. Here we report the structure of a thermostabilized human A1 receptor at 3.3 Å resolution with PSB36, an A1-selective xanthine-based antagonist. This is compared with structures of the A2A receptor with PSB36 (2...
July 3, 2017: Structure
https://www.readbyqxmd.com/read/28710541/injury-induced-purinergic-signalling-molecules-upregulate-pluripotency-gene-expression-and-mitotic-activity-of-progenitor-cells-in-the-zebrafish-retina
#13
Matías P Medrano, Claudio A Bejarano, Ariadna G Battista, Graciela D Venera, Ramón O Bernabeu, Maria Paula Faillace
Damage in fish activates retina repair that restores sight. The purinergic signalling system serves multiple homeostatic functions and has been implicated in cell cycle control of progenitor cells in the developing retina. We examined whether changes in the expression of purinergic molecules were instrumental in the proliferative phase after injury of adult zebrafish retinas with ouabain. P2RY1 messenger RNA (mRNA) increased early after injury and showed maximal levels at the time of peak progenitor cell proliferation...
July 14, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28710007/toxoplasmosis-treatment-with-diphenyl-diselenide-in-infected-mice-modulates-the-activity-of-purinergic-enzymes-and-reduces-inflammation-in-spleen
#14
Pedro H Doleski, Maura V Ten Caten, Daniela F Passos, Lívia G Castilhos, Daniela B R Leal, Vanessa S Machado, Nathieli B Bottari, Fernanda F Vogel, Ricardo E Mendes, Aleksandro Schafer da Silva
Toxoplasma gondii, an intracellular protozoan, may cause chronic infection in the brain tissue of the host inducing a systemic pro-inflammatory profile. Chronic infections can induce numerous physiological changes, such as alterations in the immune and oxidative profiles. Diphenyl diselenide (PhSe)2, an organoselenium compound, has shown antioxidant and immunomodulatory activities in recent studies. So, the aim of this study was to investigate the activity of purinergic enzymes and reactive oxygen species (ROS) in serum and spleen of mice chronically infected by T...
July 12, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28708827/deciphering-the-regulation-of-p2x4-receptor-channel-gating-by-ivermectin-using-markov-models
#15
Laurent Mackay, Hana Zemkova, Stanko S Stojilkovic, Arthur Sherman, Anmar Khadra
The P2X4 receptor (P2X4R) is a member of a family of purinergic channels activated by extracellular ATP through three orthosteric binding sites and allosterically regulated by ivermectin (IVM), a broad-spectrum antiparasitic agent. Treatment with IVM increases the efficacy of ATP to activate P2X4R, slows both receptor desensitization during sustained ATP application and receptor deactivation after ATP washout, and makes the receptor pore permeable to NMDG+, a large organic cation. Previously, we developed a Markov model based on the presence of one IVM binding site, which described some effects of IVM on rat P2X4R...
July 14, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28705804/loss-of-nitric-oxide-mediated-inhibition-of-purine-neurotransmitter-release-in-the-colon-in-the-absence-of-interstitial-cells-of-cajal
#16
Leonie Durnin, Andrea Lees, Sheerien Manzoor, Kent C Sasse, Kenton M Sanders, Violeta N Mutafova-Yambolieva
Regulation of colonic motility depends upon the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor α-positive (PDGFRα(+)) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit(W)/Kit(W-v) (W/W(v) ) mice that display lesions in ICC-IM along the gastrointestinal tract...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28702845/regulation-of-cardiac-ca-2-and-ion-channels-by-shear-mechanotransduction
#17
REVIEW
Joon-Chul Kim, Min-Jeong Son, Jun Wang, Sun-Hee Woo
Cardiac contraction is controlled by a Ca(2+) signaling sequence that includes L-type Ca(2+) current-gated opening of Ca(2+) release channels (ryanodine receptors) in the sarcoplasmic reticulum (SR). Local Ca(2+) signaling in the atrium differs from that in the ventricle because atrial myocytes lack transverse tubules and have more abundant corbular SR. Myocardium is subjected to a variety of forces with each contraction, such as stretch, shear stress, and afterload, and adapts to those mechanical stresses...
July 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28701358/mechanism-of-action-of-the-anti-inflammatory-connexin43-mimetic-peptide-jm2
#18
J Matthew Rhett, Bennett W Calder, Stephen A Fann, Heather Bainbridge, Robert G Gourdie, Michael J Yost
Connexin-based therapeutics have shown the potential for therapeutic efficacy in improving wound healing. Our previous work demonstrated that the connexin43 (Cx43)-mimetic peptide JM2 reduced the acute inflammatory response to a submuscular implant model by inhibiting purinergic signaling. Given the prospective application in improving tissue engineered construct tolerance that these results indicated, we sought to determine the mechanism of action for JM2 in the present study. Using confocal microscopy, a gap-FRAP cell communication assay, and an ethidium bromide uptake assay of hemichannel function we found that the peptide reduced cell-surface Cx43 levels, Cx43 gap junction (GJ) size, GJ communication, and hemichannel activity...
July 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28699505/tackling-chronic-pain-and-inflammation-through-the-purinergic-system
#19
Giulia Magni, Daniele Riccio, Stefania Ceruti
The purinergic system is composed of purine and pyrimidine transmitters, of the enzymes that modulate the interconversion of nucleotides and nucleosides, of the membrane transporters that control their extracellular concentrations, and of the many receptor subtypes that are responsible for their cellular responses. The components of this system are ubiquitously localized in all tissues and organs, and their involvement in several physiological conditions has been clearly demonstrated. Moreover, extracellular purine and pyrimidine concentrations raise several folds under pathological conditions like tissue damage, ischemia, and inflammation, which suggest that this signaling system might contribute both to disease outcome and, possibly, to its tentative resolution...
July 10, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28697378/changes-in-phagocytosis-and-potassium-channel-activity-in-microglia-of-5xfad-mice-indicate-alterations-in-purinergic-signaling-in-a-mouse-model-of-alzheimer-s-disease
#20
Stefan Wendt, Meron Maricos, Natascha Vana, Niklas Meyer, Dilansu Guneykaya, Marcus Semtner, Helmut Kettenmann
As the immunocompetent cells of the central nervous system, microglia accumulate at amyloid beta plaques in Alzheimer's disease (AD) and acquire a morphological phenotype of activated microglia. Recent functional studies, however, indicate that in mouse models of amyloidosis and AD, these cells are rather dysfunctional indicated by a reduced phagocytic activity. Here, we report that this reduction in phagocytic activity is associated with perturbed purinergic receptor signaling, since phagocytosis could be stimulated by P2Y6 receptor activation in control, but not in 5xFAD transgenic animals, an animal model of amyloid deposition...
June 8, 2017: Neurobiology of Aging
keyword
keyword
81978
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"