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P2 Receptors

Binbin Yao, Sha Zhu, Xinyu Xu, Ninghan Feng, Yaping Tian, Nandi Zhou
An ultrasensitive electrochemical detection of the androgen receptor (AR) was developed based on the protection of a DNA duplex by the AR from restriction endonuclease-mediated digestion and a subsequent hybridization chain reaction (HCR). Two partially complementary DNA probes P1 and P2 were designed to form an androgen receptor binding probe (ARBP) through hybridization. The ARBP contains a duplex at one end and two single-stranded tails at the other end. The duplex part containing the recognition sites of the AR and NspI restriction endonuclease was immobilized on an Au electrode, whereas the single-stranded parts served as capture probes to activate the HCR...
February 15, 2019: Analyst
Corinna Pietsch, Uwe G Liebert
BACKGROUND: Sapovirus is a common cause of self-limiting diarrhea. In immunocompromised individuals chronic infections occur, but are incompletely investigated. OBJECTIVES: To investigate viral evolution in immunocompromised hosts during chronic sapovirus infection. STUDY DESIGN: From January 2010 to September 2018 stool samples of 5333 in-patients were analyzed for the presence of sapovirus RNA by real-time RT-PCR. In follow-up samples of chronic diarrhea cases nucleic acid sequencing of sapovirus genomes was performed...
February 7, 2019: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
Fang Bian, Xiao-Yan Yang, Gao Xu, Tao Zheng, Si Jin
The NLRP3 inflammasome, a multiprotein cytosolic complex that activates the IL-1 family of cytokines, plays an important role in atherosclerosis (AS). High-sensitivity c-reactive protein (hs-CRP) is widely recognized as a major cardiovascular risk predictor and recent studies name NLRP3 as a predictor of CRP levels. Mounting evidence has indicated that subendothelial retention of apolipoprotein B100-containing lipoproteins, such as low-density lipoprotein (LDL), is the initial step of atherogenesis, and is usually termed the "response to retention hypothesis...
2019: Frontiers in Pharmacology
Natiele Carla da Silva Ferreira, Luiz Anastacio Alves, Rômulo José Soares-Bezerra
BACKGROUND: Extracellular purines and pyrimidines have important physiological functions in mammals. Purines and pyrimidines act on P1 and P2 purinergic receptors, which are widely expressed in the plasma membrane in various cell types. P2 receptors act as important therapeutic targets and are associated with several disorders, such as pain, neurodegeneration, cancer, inflammation, and thrombosis. However, the use of antagonists for P2 receptors in clinical therapy, with the exception of P2Y12, is a great challenge...
February 12, 2019: Current Drug Targets
Juyeon Ko, Jongyun Myeong, Young-Cheul Shin, Insuk So
Transient receptor potential canonical (TRPC) 4 and TRPC5 channels are modulated by the Gαq -PLC pathway. Since phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 ) maintains TRPC4 and TRPC5 channel function, the Gαq -PLC pathway inhibits channel activity by depleting PI(4,5)P2 . Here we investigated the difference in PI(4,5)P2 sensitivity between homomeric and heteromeric TRPC channels. First, by using a Danio rerio voltage-sensing phosphatase (DrVSP), we show that PI(4,5)P2 dephosphorylation robustly inhibits TRPC4α, TRPC4β, and TRPC5 homotetramer currents and also TRPC1/4α, TRPC1/4β, and TRPC1/5 heterotetramer currents...
February 12, 2019: Scientific Reports
Wenjun Zhang, Yuguo Liu, Yi Sun, Zengxu Liu
OBJECTIVES: The aim of this study was to determine the role of microencapsulated olfactory ensheathing cell (MC-OEC) transplantation in rats with sciatic nerve injury-induced pain, and its relationship with P2 × 7 receptor expression in the L4-5 spinal cord segment. METHODS: Olfactory bulb tissues of healthy Sprague Dawley (SD) rats were collected to culture olfactory ensheathing cells using differential attachment methods. Forty-eight healthy SD rats were randomly assigned to four groups: the sham, chronic constriction injury (CCI), olfactory ensheathing cell (OEC), and MC-OEC groups...
February 9, 2019: Neuroscience Letters
Maria A Battistone, Maria Merkulova, Yoo-Jin Park, Maria A Peralta, Flavia Gombar, Dennis Brown, Sylvie Breton
KEY POINTS: In the epididymis, elaborate communication networks between epithelial cells are important to establish an optimal acidic luminal environment for the maturation and storage of spermatozoa, which is essential for male fertility. Proton secretion by epididymal clear cells is achieved via the proton pumping V-ATPase located in their apical membrane. Here, we dissect the molecular mechanisms by which clear cells respond to luminal ATP and adenosine to modulate their acidifying activity via the adenosine receptor ADORA2B and the pH-sensitive ATP receptor P2 × 4...
February 12, 2019: Journal of Physiology
M J Dickson, S K Kvidera, E A Horst, C E Wiley, E J Mayorga, J Ydstie, G A Perry, L H Baumgard, A F Keating
Lipopolysaccharide (LPS) administration causes immunoactivation, which negatively affects production and fertility, but experimental exposure via an acute bolus is unlikely to resemble natural infections. Thus, the objectives were to characterize effects of chronic endotoxemia on production parameters and follicular development in estrous-synchronized lactating cows. Eleven Holstein cows (169 ± 20 d in milk; 681 ± 16 kg of body weight) were acclimated to their environmental surroundings for 3 d and then enrolled in 2 experimental periods (P)...
February 6, 2019: Journal of Dairy Science
Barbara Cacciari, Pamela Crepaldi, Chun Yan Cheng, Elena Bossi, Giampiero Spalluto, Stephanie Federico, Kenneth A Jacobson, Marco Cattaneo
BACKGROUND: Platelet aggregation plays a pathogenic role in the development of arterial thrombi, which are responsible for common diseases caused by thrombotic arterial occlusion, such as myocardial infarction and stroke. Much efforts is directed toward developing platelet aggregation inhibitors that act through several mechanisms: the main antiplatelet family of COX-inhibitors, phosphodiesterase inhibitors, and thrombin inhibitors. Recently, the important role in the platelet aggregation of adenosine diphosphate (ADP)-activated P2Y12 and P2Y1 receptors, G-protein coupled receptors of the P2 purinergic family, has emerged, and their inhibitors are explored as potential therapeutic antithrombotics...
February 8, 2019: Medicinal Chemistry
Ke-Zhong Shen, Adam C Munhall, Steven W Johnson
We reported recently that ligand-gated ATP-sensitive K+ (K-ATP) current is potentiated by AMP-activated protein kinase (AMPK) in rat substantia nigra compacta (SNC) dopamine neurons. Because phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) regulates K-ATP current, we explored the hypothesis that changes in PI(4,5)P2 modify the ability of AMPK to augment K-ATP current. To influence PI(4,5)P2 levels, we superfused brain slices with phospholipase C (PLC) activators and inhibitors while recording whole-cell currents in SNC dopamine neurons...
March 1, 2019: Brain Research
Lumei Huang, Lilla Otrokocsi, Beáta Sperlágh
The purinergic signaling system, including P2 receptors, plays an important role in various central nervous system (CNS) disorders. Over the last few decades, a substantial amount of accumulated data suggest that most P2 receptor subtypes (P2 × 1, 2, 3, 4, 6, and 7, and P2Y1 , 2 , 6 , 12 , and 13 ) regulate neuronal/neuroglial developmental processes, such as proliferation, differentiation, migration of neuronal precursors, and neurite outgrowth. However, only a few of these subtypes (P2 × 2, P2 × 3, P2 × 4, P2 × 7, P2Y1 , and P2Y2 ) have been investigated in the context of neurodevelopmental psychiatric disorders...
February 2, 2019: Brain Research Bulletin
Álvaro Sebastián-Serrano, Laura de Diego-García, Caterina di Lauro, Carolina Bianchi, Miguel Díaz-Hernández
Neurodegenerative diseases (ND) are a heterogeneous group of neurological disorders characterized by a progressive loss of neuronal function which results in neuronal death. Although a specific toxic factor has been identified for each ND, all of them share common pathological molecular mechanisms favouring the disease development. In the final stages of ND, patients become unable to take care of themselves and decline to a total functional incapacitation that leads to their death. Some of the main factors which contribute to the disease progression include proteasomal dysfunction, neuroinflammation, synaptic alterations, protein aggregation, and oxidative stress...
February 2, 2019: Brain Research Bulletin
Jodie P Goodridge, Benedikt Jacobs, Michelle L Saetersmoen, Dennis Clement, Quirin Hammer, Trevor Clancy, Ellen Skarpen, Andreas Brech, Johannes Landskron, Christian Grimm, Aline Pfefferle, Leonardo Meza-Zepeda, Susanne Lorenz, Merete Thune Wiiger, William E Louch, Eivind Heggernes Ask, Lisa L Liu, Vincent Yi Sheng Oei, Una Kjällquist, Sten Linnarsson, Sandip Patel, Kjetil Taskén, Harald Stenmark, Karl-Johan Malmberg
Inhibitory signaling during natural killer (NK) cell education translates into increased responsiveness to activation; however, the intracellular mechanism for functional tuning by inhibitory receptors remains unclear. Secretory lysosomes are part of the acidic lysosomal compartment that mediates intracellular signalling in several cell types. Here we show that educated NK cells expressing self-MHC specific inhibitory killer cell immunoglobulin-like receptors (KIR) accumulate granzyme B in dense-core secretory lysosomes that converge close to the centrosome...
January 31, 2019: Nature Communications
William F Hawse, Richard T Cattley
T-cell receptor (TCR) signaling strength is a dominant factor regulating T-cell differentiation, thymic development, and cytokine signaling. The molecular mechanisms by which TCR signal strength is transduced to downstream signaling networks remains ill defined. Using computational modeling, biochemical assays, and imaging flow cytometry, we found here that TCR signal strength differentially generates phosphatidylinositol species. Weak TCR signals generated elevated phosphatidylinositol 4,5-bisphosphate (Pi(4,5)P2) and reduced phosphatidylinositol (3,4,5)-trisphosphate (PIP3) levels, whereas strong TCR signals reduced Pi(4,5)P2 and elevated PIP3 levels...
January 28, 2019: Journal of Biological Chemistry
Joel Linden, Friedrich Koch-Nolte, Gerhard Dahl
ATP, NAD+ , and nucleic acids are abundant purines that, in addition to having critical intracellular functions, have evolved extracellular roles as danger signals released in response to cell lysis, apoptosis, degranulation, or membrane pore formation. In general ATP and NAD+ have excitatory and adenosine has anti-inflammatory effects on immune cells. This review focuses on recent advances in our understanding of purine release mechanisms, ectoenzymes that metabolize purines (CD38, CD39, CD73, ENPP1, and ENPP2/autotaxin), and signaling by key P2 purinergic receptors (P2X7, P2Y2, and P2Y12)...
January 24, 2019: Annual Review of Immunology
Matthew P Wilson, Barbara Plecko, Philippa B Mills, Peter T Clayton
Vitamin B6 is present in our diet in many forms however only pyridoxal 5'-phosphate (PLP) can function as a cofactor for enzymes. The intestine absorbs non-phosphorylated B6 vitamers, which are converted by specific enzymes to the active PLP form. The role of PLP is enabled by its reactive aldehyde group. Pathways reliant on PLP include amino acid and neurotransmitter metabolism, folate and 1-carbon metabolism, protein and polyamine synthesis, carbohydrate and lipid metabolism, mitochondrial function and erythropoiesis...
January 22, 2019: Journal of Inherited Metabolic Disease
Michael G Leitner, Veronika Thallmair, Bettina U Wilke, Valentin Neubert, Yannick Kronimus, Christian R Halaszovich, Dominik Oliver
Phospholipase Cβ (PLCβ)-induced depletion of phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2 ) transduces a plethora of signals into cellular responses. Importance and diversity of PI(4,5)P2 -dependent processes led to strong need for biosensors of physiological PI(4,5)P2 dynamics applicable in live-cell experiments. Membrane PI(4,5)P2 can be monitored with fluorescently-labelled phosphoinositide (PI) binding domains that associate to the membrane depending on PI(4,5)P2 levels. The pleckstrin homology domain of PLCδ1 (PLCδ1-PH) and the C-terminus of tubby protein (tubbyCT ) are two such sensors widely used to study PI(4,5)P2 signaling...
March 2019: Biochimica et biophysica acta. Molecular and cell biology of lipids
Elsa Fabbretti
Peripheral stimuli are transduced by specific receptors expressed by sensory neurons and are further processed in the dorsal horn of spinal cord before to be transmitted to the brain. While relative few receptor subtypes mediate the initial depolarisation of sensory neurons, an impressive number of molecules and ion channels integrate these inputs into coded signals. Soluble mediators and ambient conditions further shape these processes, potentially triggering peripheral and central sensitisation, or sensory downregulation...
January 17, 2019: Brain Research Bulletin
Haiping Liu, Ahmed Kabrah, Malini Ahuja, Shmuel Muallem
The receptor-evoked Ca2+ signal in secretory epithelia mediate many cellular functions essential for cell survival and their most fundamental functions of secretory granules exocytosis and fluid and electrolyte secretion. Ca2+ influx is a key component of the receptor-evoked Ca2+ signal in secretory cell and is mediated by both TRPC and the STIM1-activated Orai1 channels that mediates the Ca2+ release-activated current (CRAC) Icrac . The core components of the receptor-evoked Ca2+ signal are assembled at the ER/PM junctions where exchange of materials between the plasma membrane and internal organelles take place, including transfer of lipids and Ca2+ ...
December 31, 2018: Cell Calcium
Pelin Cengiz, Dila Zafer, Jayadevi H Chandrashekhar, Vishal Chanana, Jacob Bogost, Alex Waldman, Becca Novak, Douglas B Kintner, Peter A Ferrazzano
BACKGROUND: Neuroinflammation plays an important role in ischemic brain injury and recovery, however the interplay between brain development and the neuroinflammatory response is poorly understood. We previously described age-dependent differences in the microglial response and the effect of microglial inhibition. Here we investigate whether age-dependent microglial responses may be related to pre-injury developmental differences in microglial phenotype. METHODS: Measures of microglia morphology were quantified using semi-automated software analysis of immunostained sections from postnatal day 2 (P2), P9, P30 and P60 mice using IMARIS...
January 9, 2019: Neurochemistry International
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