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P2 Receptors

Jongyun Myeong, Juyeon Ko, Misun Kwak, Jinsung Kim, Joohan Woo, Kotdaji Ha, Chansik Hong, Dongki Yang, Hyun Jin Kim, Ju-Hong Jeon, Insuk So
The transient receptor potential canonical (TRPC) 1 channel is widely distributed in mammalian cells and is involved in many physiological processes. TRPC1 is primarily considered a regulatory subunit that forms heterotetrameric channels with either TRPC4 or TRPC5 subunits. Here, we suggest that the regulation of TRPC1/4 and TRPC1/5 heterotetrameric channels by the Gαq -PLCβ pathway is self-limited and dynamically mediated by Gαq and PI(4,5)P2 . We provide evidence indicating that Gαq protein directly interacts with either TRPC4 or TRPC5 of the heterotetrameric channels to permit activation...
August 14, 2018: Scientific Reports
Tobias Eckrich, Kerstin Blum, Ivan Milenkovic, Jutta Engel
Before the onset of hearing, which occurs around postnatal day 12 (P12) in mice, inner hair cells (IHCs) of the immature cochlea generate sound-independent Ca2+ action potentials (APs), which stimulate the auditory pathway and guide maturation of neuronal circuits. During these early postnatal days, intercellular propagating Ca2+ waves elicited by ATP-induced ATP release are found in inner supporting cells (ISCs). It is debated whether IHCs are able to fire Ca2+ APs independently or require a trigger by an ISC Ca2+ wave...
2018: Frontiers in Molecular Neuroscience
Gergely Kovács, Zsuzsanna Környei, Krisztina Tóth, Mária Baranyi, János Brunner, Máté Neubrandt, Ádám Dénes, Beáta Sperlágh
The P2X7R protein, a P2 type purinergic receptor functioning as a non-selective cation channel, is expressed in different cell types of the central nervous system in several regions of the brain. The activation of the P2X7R protein by ATP modulates excitatory neurotransmission and contributes to microglial activation, apoptosis and neuron-glia communication. Zinc is an essential micronutrient that is highly concentrated in the synaptic vesicles of glutamatergic hippocampal neurons where free zinc ions released into the synaptic cleft alter glutamatergic signal transmission...
July 30, 2018: Cell Calcium
Muhammad Tahir Khan, Jan Deussing, Yong Tang, Peter Illes
Whole-cell patch clamp recordings demonstrated that in the dentate gyrus (DG) as well as in the CA3 area of mouse hippocampal slices the prototypic P2 × 7 receptor (R) agonist dibenzoyl-ATP (Bz-ATP) induced inward current responses both in neurons and astrocytes. Whereas the selective P2 × 7R antagonist A438079 strongly inhibited both neuronal and astrocytic currents, a combination of ionotropic glutamate receptor (CNQX, AP-5) and GABAA -R (gabazine) antagonists depressed the Bz-ATP-induced current responses in the DG (granule cells) and CA3 neurons only...
August 8, 2018: Brain Research Bulletin
Sae Byul Lee, Seung Sang Ko, Chan Heun Park, Seok Jin Nam, Jung Eun Choi, Yong Sik Jung, Woo-Chan Park, Byung Ho Son
PURPOSE: Advances in breast cancer treatment have contributed to marked improvements in patient outcomes over the past three decades. This study aims to chronologically evaluate the survival of patients with breast cancer and investigate the observed changes over time. METHODS: Statistics from the Korean National Cancer Registry, based on all 60,571 patients with invasive breast cancer during the 21 year period, were analyzed. We divided the study interval into four periods (P1: 1988-1992, P2: 1993-1997, P3: 1998-2002, P4: 2003-2008)...
August 7, 2018: Breast Cancer Research and Treatment
Andrew M Riley, Judith Unterlass, Vera Konieczny, Colin W Taylor, Thomas Helleday, Barry V L Potter
Diphosphoinositol phosphates (PP-InsPs) are inositol phosphates (InsPs) that contain PP (diphosphate) groups. Converting a phosphate group in an InsP into a diphosphate has been reported to enhance affinity for some binding proteins. We synthesised 1-PP-Ins(4,5)P2 , the first diphosphate analogue of the intracellular signalling molecule InsP3 , and examined its effects on InsP3 receptors, which are intracellular Ca2+ channels. 1-PP-Ins(4,5)P2 was indistinguishable from InsP3 in its ability to bind to and activate type 1 InsP3 receptors, indicating that the diphosphate modification of InsP3 affected neither affinity nor efficacy...
July 1, 2018: MedChemComm
Lian Duan, Guo-Huang Hu, Yi-Jin Li, Cheng-Liang Zhang, Meng Jiang
Pulmonary arterial hypertension (PAH) is a progressive disease that ultimately leads to right heart failure and death. Current strategies are ineffective to prevent and cure PAH, especially in those who undergo cardiopulmonary bypass. P2 × 7 receptors (P2 × 7Rs) have been implied to participate in the pathogenesis of PAH and injuries induced by ischemia-reperfusion (IR). In the present study, we aimed to assess the potential therapeutic effects of anti-P2 × 7Rs on PAH and IR-induced lung injuries in rats and explore their underlying cellular and molecular mechanisms...
August 2, 2018: Molecular Immunology
Nicola De Franceschi, Mitro Miihkinen, Hellyeh Hamidi, Jonna Alanko, Anja Mai, Laura Picas, Camilo Guzmán, Daniel Lévy, Peter Mattjus, Benjamin T Goult, Bruno Goud, Johanna Ivaska
Integrin transmembrane receptors control a wide range of biological interactions by triggering the assembly of large multiprotein complexes at their cytoplasmic interface. Diverse methods have been used to investigate interactions between integrins and intracellular proteins, and predominantly include peptide-based pull-downs and biochemical immuno-isolations from detergent-solubilized cell lysates. However, quantitative methods to probe integrin-protein-protein interactions in a more biologically relevant context where the integrin is embedded within a lipid bilayer have been lacking...
August 2, 2018: Journal of Cell Science
Thomas Dahl Nissen, Christina Brock, Jens Lykkesfeldt, Erik Lindström, Leif Hultin
BACKGROUND: Cerebral evoked potentials (CEP) induced by colorectal distension (CRD) in conscious rats provides a novel method in studies of visceral sensitivity. The aim of this study was to explore the pharmacological effect on CEP of compounds known to reduce the visceromotor response to CRD. METHODS: Epidural electrodes were chronically implanted in eight female Sprague-Dawley rats. Evoked potentials were elicited by colorectal rapid balloon distensions (100 ms, 80 mmHg) and the effect of WIN55 (cannabinoid CB receptor agonist), clonidine (adrenergic α2 receptor agonist), MPEP (mGluR5 receptor antagonist), pregabalin (ligand of α2 δ subunits in voltage-gated calcium channels) and baclofen (GABA-B receptor agonist) on amplitudes and latency of CEP were determined...
July 27, 2018: Neuropharmacology
Liqian Zhu, Clinton Jones, Gaiping Zhang
Macrophages are crucial members of the mononuclear phagocyte system essential to protect the host from invading pathogens and are central to the inflammatory response with their ability to acquire specialized phenotypes of inflammatory (M1) and anti-inflammatory (M2) and to produce a pool of inflammatory mediators. Equipped with a broad range of receptors, such as Toll-like receptor 4 (TLR4), CD14, and Fc gamma receptors (Fc γ Rs), macrophages can efficiently recognize and phagocytize invading pathogens and secrete cytokines by triggering various secondary signaling pathways...
2018: Journal of Immunology Research
Dujuan Huang, Junna Yang, XiaoHong Liu, Li He, Xiaomei Luo, Hong Tian, Tao Xu, Junwei Zeng
Purinergic signaling in spinal cord microglia plays an important role in the pathogenesis of neuropathic pain. Among all P2 receptors, P2Y6 receptor is expressed in rat dorsal spinal cord. However, it's not clear that the role of P2Y6 receptor in the chronic constriction injury (CCI) model of neuropathic pain rats. We evaluated the effect of repeated intrathecal administration of MRS2578 (selective P2Y6 receptor antagonist) on CCI-induced nociceptive behaviors in rats. After CCI, MRS2578 (10-11 -10-4  M) was administration...
July 23, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Ido Somekh, Benjamin Marquardt, Yanshan Liu, Meino Rohlfs, Sebastian Hollizeck, Musa Karakukcu, Ekrem Unal, Ebru Yilmaz, Turkan Patiroglu, Murat Cansever, Shirly Frizinsky, Vicktoria Vishnvenska-Dai, Erez Rechavi, Tali Stauber, Amos J Simon, Atar Lev, Christoph Klein, Daniel Kotlarz, Raz Somech
PURPOSE: RAS guanyl-releasing protein 1 (RASGRP1) deficiency has recently been shown to cause a primary immunodeficiency (PID) characterized by CD4+ T cell lymphopenia and Epstein-Barr virus (EBV)-associated B cell lymphoma. Our report of three novel patients widens the scope of RASGRP1 deficiency by providing new clinical and immunological insights on autoimmunity, immune cell development, and predisposition to lymphoproliferative disease. METHODS: One patient of Turkish origin (P1) and two Palestinian patients (P2, P3) were evaluated for immunodeficiency...
July 20, 2018: Journal of Clinical Immunology
Tali Fishman Jacob, Vijay Singh, Mudit Dixit, Tamar Ginsburg-Shmuel, Begoña Fonseca, Jesus Pintor, Moussa B H Youdim, Dan T Major, Orly Weinreb, Bilha Fischer
Extracellular nucleotides can regulate the production/drainage of the aqueous humor via activation of P2 receptors, thus affecting the intraocular pressure (IOP). We evaluated 5-OMe-UDP(α-B), 1A, a potent P2Y6-receptor agonist, for reducing IOP and treating glaucoma. Cell viability in the presence of 1A was measured using [3-(4, 5-dimethyl-thiazol-2-yl) 2, 5-diphenyl-tetrazolium bromide] (MTT) assay in rabbit NPE ciliary non-pigmented and corneal epithelial cells, human retinoblastoma, and liver Huh7 cells...
July 17, 2018: Purinergic Signalling
Thanh Sang Vo, Young-Sang Kim, Dai Hung Ngo, Phuong Uyen Le, So-Yeon Kim, Se-Kwon Kim
In this study, the suppressive effects of peptides P1 (LDAVNR) and P2 (MMLDF) from enzymatic hydrolysate of Spirulina maxima on mast cell degranulation was elucidated. It was revealed that P1 and P2 exhibited significant inhibition on cell degranulation via decreasing β-hexosaminidase release at concentration of 200 μM. Moreover, the inhibitory effects of P1 and P2 on expression and production of interleukin (IL)-13 were evidenced. Furthermore, peptide treatment caused a remarkable inhibition on the phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) including ERK, p38, and JNK...
July 22, 2018: International Journal of Biological Macromolecules
Chun Yang, Andrei Larin, James T McKenna, Kenneth A Jacobson, Stuart Winston, Robert E Strecker, Anna Kalinchuk, Radhika Basheer, Ritchie E Brown
The functions of purinergic P2 receptors (P2Rs) for extracellular adenosine triphosphate (ATP) are poorly understood. Here, for the first time, we show that activation of P2Rs in an important arousal region, the basal forebrain (BF), promotes wakefulness, whereas inhibition of P2Rs promotes sleep. Infusion of a non-hydrolysable P2R agonist, ATP-γ-S, into mouse BF increased wakefulness following sleep deprivation. ATP-γ-S depolarized BF cholinergic and cortically-projecting GABAergic neurons in vitro, an effect blocked by antagonists of ionotropic P2Rs (P2XRs) or glutamate receptors...
July 16, 2018: Scientific Reports
Francesco Di Virgilio, Alba Clara Sarti, Simonetta Falzoni, Elena De Marchi, Elena Adinolfi
Modulation of the biochemical composition of the tumour microenvironment is a new frontier of cancer therapy. Several immunosuppressive mechanisms operate in the milieu of most tumours, a condition that makes antitumour immunity ineffective. One of the most potent immunosuppressive factors is adenosine, which is generated in the tumour microenvironment owing to degradation of extracellular ATP. Accruing evidence over the past few years shows that ATP is one of the major biochemical constituents of the tumour microenvironment, where it acts at P2 purinergic receptors expressed on both tumour and host cells...
July 13, 2018: Nature Reviews. Cancer
Hsin-Yung Yen, Kin Kuan Hoi, Idlir Liko, George Hedger, Michael R Horrell, Wanling Song, Di Wu, Philipp Heine, Tony Warne, Yang Lee, Byron Carpenter, Andreas Plückthun, Christopher G Tate, Mark S P Sansom, Carol V Robinson
G-protein-coupled receptors (GPCRs) are involved in many physiological processes and are therefore key drug targets1 . Although detailed structural information is available for GPCRs, the effects of lipids on the receptors, and on downstream coupling of GPCRs to G proteins are largely unknown. Here we use native mass spectrometry to identify endogenous lipids bound to three class A GPCRs. We observed preferential binding of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2 ) over related lipids and confirm that the intracellular surface of the receptors contain hotspots for PtdIns(4,5)P2 binding...
July 2018: Nature
Sruthi S Balakrishnan, Urbashi Basu, Dhananjay Shinde, Rajan Thakur, Manish Jaiswal, Padinjat Raghu
The activation of phospholipase C (PLC) is a conserved mechanism of receptor activated cell signaling at the plasma membrane. PLC hydrolyzes the minor membrane lipid phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2 ] and continued signaling requires the resynthesis and availability of PI(4,5)P2 at the plasma membrane. PI(4,5)P2 is synthesized by the phosphorylation of phosphatidylinositol-4-phosphate (PI4P). Thus, a continuous supply of PI4P is essential to support ongoing PLC signaling. While the enzyme PI4KA has been identified to perform this function in cultured mammalian cells, its function in the context of an in vivo physiological model has not been established...
July 6, 2018: Journal of Cell Science
Manimaran Ramani, Ranjit Kumar, Brian Halloran, Charitharth Vivek Lal, Namasivayam Ambalavanan, Lori L McMahon
Preterm infants often require prolonged oxygen supplementation and are at high risk of neurodevelopmental impairment. We recently reported that adult mice exposed to neonatal hyperoxia (postnatal day [P] 2 to 14) had spatial navigation memory deficits associated with hippocampal shrinkage. The mechanisms by which early oxidative stress impair neurodevelopment are not known. Our objective was to identify early hyperoxia-induced alterations in hippocampal receptors and signaling pathways necessary for memory formation...
July 2, 2018: Scientific Reports
Helen P Makarenkova, Sameer B Shah, Valery I Shestopalov
Pannexins belong to a family of ATP-release channels expressed in almost all cell types. An increasing body of literature on pannexins suggests that these channels play dual and sometimes contradictory roles, contributing to normal cell function, as well as to the pathological progression of disease. In this review, we summarize our understanding of pannexin "protective" and "harmful" functions in inflammation, regeneration and mechanical signaling. We also suggest a possible basis for pannexin's dual roles, related to extracellular ATP and K+ levels and the activation of various types of P2 receptors that are associated with pannexin...
2018: Journal of Inflammation Research
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