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https://www.readbyqxmd.com/read/29077063/p2x4-receptor-dependent-ca-2-influx-in-model-human-monocytes-and-macrophages
#1
Janice A Layhadi, Samuel J Fountain
Monocytes and macrophages express a repertoire of cell surface P2 receptors for adenosine 5'-triphosphate (ATP) a damage-associated molecular pattern molecule (DAMP), which are capable of raising cytoplasmic calcium when activated. This is achieved either through direct permeation (ionotropic P2X receptors) or by mobilizing intracellular calcium stores (metabotropic P2Y receptors). Here, a side-by-side comparison to investigate the contribution of P2X4 receptor activation in ATP-evoked calcium responses in model human monocytes and macrophages was performed...
October 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29063617/ivermectin-and-its-target-molecules-shared-and-unique-modulation-mechanisms-of-ion-channels-and-receptors-by-ivermectin
#2
I-Shan Chen, Yoshihiro Kubo
Ivermectin (IVM) is an antiparasitic drug that is used worldwide and rescues hundreds of millions of people from onchocerciasis and lymphatic filariasis. It was discovered by Satoshi Ōmura and William C. Campbell, to whom the 2015 Nobel Prize in Physiology or Medicine was awarded. It kills parasites by activating glutamate-gated Cl(-) channels, and it also targets several ligand-gated ion channels and receptors, including Cys-loop receptors, P2X4 receptors and fernesoid X receptors. Recently, we found that IVM also activates a novel target, the G-protein-gated inwardly rectifying K(+) channel, and also identified the structural determinant for the activation...
October 23, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28988113/effects-of-dexamethasone-on-purinergic-signaling-in-murine-mast-cells-selective-suppression-of-p2x7-receptor-expression
#3
Kazuki Yoshida, Masaaki Ito, Yui Hoshino, Isao Matsuoka
Mast cells express many different purinergic receptors, including ionotropic P2X4 and P2X7, which recognize the accumulation of extracellular ATP released from activated and/or damaged cells. This results in the stimulation of mast cell functions. In this study, we investigated the effects of dexamethasone (Dex), an anti-inflammatory glucocorticoid widely used for the treatment of allergic disease, on purinergic receptor expression in mouse bone marrow-derived mast cells (BMMCs). Treatment of BMMCs with Dex decreased P2X7 receptor mRNA levels in a time- and concentration-dependent manner without affecting the expression of other purinergic receptor subtypes...
December 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28943285/ethanol-differentially-modulates-p2x4-and-p2x7-receptor-activity-and-function-in-bv2-microglial-cells
#4
Liana Asatryan, Olga Ostrovskaya, Dustin Lieu, Daryl L Davies
Neuroinflammation is one of the mechanisms leading to neurodegenerative brain damage induced by chronic alcohol (ethanol) exposure. Microglia play a major role in the development of innate immune responses to environmental injuries including ethanol. Adenosine 5″-triphosphate (ATP)-activated purinergic P2X receptor (P2XR) subtypes, P2X4Rs and P2X7Rs, are endogenously expressed in microglia and can modulate their activity. These 2 P2XR subtypes differ pharmacologically and functionally: 1) P2X4Rs are activated at lower (≤0...
September 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28937704/a-high-concentration-of-fatty-acids-induces-tnf-%C3%AE-as-well-as-no-release-mediated-by-the-p2x4-receptor-and-the-protective-effects-of-puerarin-in-raw264-7-cells
#5
Yun-Ming Tu, Cheng-Xin Gong, Lu Ding, Xing-Zi Liu, Tao Li, Fang-Fang Hu, Shuo Wang, Chao-Peng Xiong, Shang-Dong Liang, Hong Xu
Circulating levels of free fatty acids (FFAs) are often found to be increased in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS). High plasma FFA levels may give rise to maladaptive macrophage activation and promote inflammatory responses, which has been proposed as a potential mechanism for the development of DM and MS. P2X4 receptor (P2X4R), a ligand-gated cation channel activated by extracellular adenosine triphosphate (ATP), plays a primary role in the regulation of inflammatory responses...
September 22, 2017: Food & Function
https://www.readbyqxmd.com/read/28863817/regulation-of-p2x-purinergic-receptor-signaling-by-cholesterol
#6
Ruth D Murrell-Lagnado
P2X receptors are cation-selective channels that are activated by the binding of extracellular ATP. They have a high permeability to Ca(2+), Na(+), and K(+) and are expressed widely throughout the nervous, immune, cardiovascular, skeletal, gastrointestinal, respiratory, and endocrine systems. Seven mammalian subtypes of P2X receptor subunits have been identified, P2X1-7, and those that function as homotrimeric receptors (P2X1, 2, 3, 4, and 7) are targeted to lipid rafts, although they show limited resistance to solubilization by Triton X-100...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28751018/deletion-of-the-p2x4-receptor-is-neuroprotective-acutely-but-induces-a-depressive-phenotype-during-recovery-from-ischemic-stroke
#7
Rajkumar Verma, Chunxia G Cronin, Jacob Hudobenko, Venugopal R Venna, Louise D McCullough, Bruce T Liang
INTRODUCTION: Acute ischemic injury leads to severe neuronal loss. One of the key mechanisms responsible for this effect is inflammation, which is characterized by the activation of myeloid cells, including resident microglia and infiltrating monocytes/macrophages. P2X4 receptors (P2X4Rs) present on these immune cells modulate the inflammatory response. For example, excessive release of adenosine triphosphate during acute ischemic stroke triggers stimulation of P2X4Rs, leading to myeloid cell activation and proliferation and further exacerbating post-ischemic inflammation...
November 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28728214/p2x-receptor-channels-in-chronic-pain-pathways
#8
REVIEW
Louis-Philippe Bernier, Ariel R Ase, Philippe Séguéla
Chronic pain is a highly prevalent debilitating condition for which treatment options remain limited for many patients. Ionotropic ATP signaling through excitatory and calcium-permeable P2X receptor-channels is now rightfully considered as a critical player in pathological pain generation and maintenance, therefore their selective targeting represents a therapeutic opportunity with promising yet untapped potential. Recent advances in the structural, functional and pharmacological characterization of rodent and human ATP-gated P2X receptor-channels have shed brighter light on the role of specific subtypes in the pathophysiology of chronic inflammatory, neuropathic or cancer pain...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28708827/deciphering-the-regulation-of-p2x4-receptor-channel-gating-by-ivermectin-using-markov-models
#9
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 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28687864/stressed-podocytes-mechanical-forces-sensors-signaling-and-response
#10
REVIEW
Karlhans Endlich, Felix Kliewe, Nicole Endlich
Increased glomerular capillary pressure (glomerular hypertension) and increased glomerular filtration rate (glomerular hyperfiltration) have been proven to cause glomerulosclerosis in animal models and are likely to be operative in patients. Since podocytes cover the glomerular basement membrane, they are exposed to tensile stress due to circumferential wall tension and to fluid shear stress arising from filtrate flow through the narrow filtration slits and through Bowman's space. In vitro evidence documents that podocytes respond to tensile stress as well as to fluid shear stress...
August 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28677119/atp-evokes-ca-2-signals-in-cultured-foetal-human-cortical-astrocytes-entirely-through-g-protein-coupled-p2y-receptors
#11
Margit S Muller, Colin W Taylor
Extracellular ATP plays important roles in coordinating the activities of astrocytes and neurons, and aberrant signalling is associated with neurodegenerative diseases. In rodents, ATP stimulates opening of Ca(2+) -permeable channels formed by P2X receptor subunits in the plasma membrane. It is widely assumed, but not verified, that P2X receptors also evoke Ca(2+) signals in human astrocytes. Here, we directly assess this hypothesis. We showed that cultured foetal cortical human astrocytes express mRNA for several P2X receptor subunits (P2X4 , P2X5 , P2X6 ) and G protein-coupled P2Y receptors (P2Y1 , P2Y2 , P2Y6 , P2Y11 )...
July 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28668500/toll-like-receptor-4-p38-mapk-signaling-in-the-dorsal-horn-contributes-to-p2x4-receptor-activation-and-bdnf-over-secretion-in-cancer-induced-bone-pain
#12
Xiao-Wen Meng, Jian-Ling Gao, Jian-Ling Zuo, Li-Na Wang, Si-Lan Liu, Xiao-Hong Jin, Ming Yao, Michael Namaka
Our previous research suggested that the P2X4 receptor (P2X4R) expression in microglia was involved in the activation of toll-like receptor-4 (TLR4) in the dorsal horn in the rat model of cancer induced bone pain (CIBP). In this study, we focused on whether TLR4- mitogen-activated protein kinases, p38 (p38 MAPK) contributes to P2X4R activation and brain-derived neurotrophic factor (BDNF) over-secretion in CIBP. In in vitro experiment, the results showed that BDNF expression evoked by ATP stimulation was dependent on TLR4-p38...
June 28, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28588493/p2x4-receptor-function-in-the-nervous-system-and-current-breakthroughs-in-pharmacology
#13
REVIEW
Leanne Stokes, Janice A Layhadi, Lucka Bibic, Kshitija Dhuna, Samuel J Fountain
Adenosine 5'-triphosphate is a well-known extracellular signaling molecule and neurotransmitter known to activate purinergic P2X receptors. Information has been elucidated about the structure and gating of P2X channels following the determination of the crystal structure of P2X4 (zebrafish), however, there is still much to discover regarding the role of this receptor in the central nervous system (CNS). In this review we provide an overview of what is known about P2X4 expression in the CNS and discuss evidence for pathophysiological roles in neuroinflammation and neuropathic pain...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28554730/synthesis-and-preliminary-biological-evaluation-of-radiolabeled-5-bdbd-analogs-as-new-candidate-pet-radioligands-for-p2x4-receptor
#14
Min Wang, Mingzhang Gao, Jill A Meyer, Jonathan S Peters, Hamideh Zarrinmayeh, Paul R Territo, Gary D Hutchins, Qi-Huang Zheng
P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a specific P2X4 receptor antagonist, as a scaffold. 5-(3-Hydroxyphenyl)-1-[(11)C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[(11)C]Me-5-BDBD analog, [(11)C]9) and 5-(3-Bromophenyl)-1-[(11)C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[(11)C]Me-5-BDBD, [(11)C]8c) were prepared from their corresponding desmethylated precursors with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with SPE in 30-50% decay corrected radiochemical yields with 370-1110GBq/µmol specific activity at EOB...
July 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28547658/time-of-day-dependent-expression-of-purinergic-receptors-in-mouse-suprachiasmatic-nucleus
#15
Julian Lommen, Anna Stahr, Marc Ingenwerth, Amira A H Ali, Charlotte von Gall
Purinergic P2X and P2Y receptors are involved in mediating intercellular signalling via purines such as adenosine triphosphate (ATP). P2X and P2Y receptors have been implicated in numerous body functions including learning, memory and sleep. All of these body functions show time-of-day-dependent variations controlled by the master circadian oscillator located in the suprachiasmatic nucleus (SCN). Evidence exists for a role of purinergic signalling in intercellular coupling within SCN. However, few studies have been performed on the expression of purinergic receptors in SCN...
May 26, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28461136/olfactory-ensheathing-cell-transplantation-inhibits-p2x4-receptor-overexpression-in-spinal-cord-injury-rats-with-neuropathic-pain
#16
Zuncheng Zheng, Xiaojing Du, Kaigang Zhang, Xiaoyu Wang, Yuexia Chen, Naifeng Kuang, Tao Fan, Baoliang Sun
Cell-based therapy is a promising strategy to alleviate neuropathic pain caused by spinal cord injury (SCI). We transplanted olfactory ensheathing cells (OECs) into SCI rats with neuropathic pain and quantitatively detected the sensory nerve function. The expression levels of P2X4 receptor (P2X4R), 200kD neurofilament heavy polypeptide (NF200), and glial fiber acidic protein (GFAP) were measured by immunofluorescence and Western blot analyses. Results showed that NF200 expression significantly increased, GFAP expression decreased, and sensory nerve function improved...
April 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28458288/neuropharmacological-study-of-atp-receptors-especially-in-the-relationship-between-glia-and-pain
#17
REVIEW
Kazuhide Inoue
A growing body of evidence indicates that extracellular ATP released or leaked from nonexcitable cells as well as neurons plays important roles in the regulation of neuronal and glial functions in the entire body through ATP receptors. ATP receptors (ionotropic P2X and metabotropic P2Y receptors) are the most abundant receptor families in living organisms. In the central nervous system, these receptors participate in the synaptic transmission and intercellular communications between neurons and glia. The glia cells are classified into three types: astrocytes; oligodendrocytes; and microglia...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28428949/p2x1-p2x4-and-p2x7-receptor-knock-out-mice-expose-differential-outcome-of-sepsis-induced-by-%C3%AE-haemolysin-producing-escherichia-coli
#18
Anne-Sofie Greve, Marianne Skals, Steen K Fagerberg, Wulf Tonnus, Svend Ellermann-Eriksen, Richard J Evans, Andreas Linkermann, Helle A Praetorius
α-haemolysin (HlyA)-producing Escherichia coli commonly inflict severe urinary tract infections, including pyelonephritis, which comprises substantial risk for sepsis. In vitro, the cytolytic effect of HlyA is mainly mediated by ATP release through the HlyA pore and subsequent P2X1/P2X7 receptor activation. This amplification of the lytic process is not unique to HlyA but is observed by many other pore-forming proteins including complement-induced haemolysis. Since free hemoglobin in the blood is known to be associated with a worse outcome in sepsis one could speculate that inhibition of P2X receptors would ameliorate the course of sepsis...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28413195/purinergic-signaling-in-microglia-in-the-pathogenesis-of-neuropathic-pain
#19
REVIEW
Kazuhide Inoue
Nerve injury often causes debilitating chronic pain, referred to as neuropathic pain, which is refractory to currently available analgesics including morphine. Many reports indicate that activated spinal microglia evoke neuropathic pain. The P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, is upregulated in spinal microglia after nerve injury by several factors, including CC chemokine receptor CCR2, the extracellular matrix protein fibronectin in the spinal cord, interferon regulatory factor 8 (IRF8) and IRF5...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28394853/targeting-brain-derived-neurotrophic-factor-in-the-medial-thalamus-for-the-treatment-of-central-poststroke-pain-in-a-rodent-model
#20
Hsi-Chien Shih, Yung-Hui Kuan, Bai-Chung Shyu
Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. An animal model of CPSP was established by an intrathalamus injection of collagenase. Mechanical and thermal allodynia was induced after lesions of the thalamic ventral basal complex in rats. Four weeks after the injection, the number of neurons decreased, the number of astrocytes, microglia, and P2X4 receptors increased, and BDNF mRNA expression increased in the brain lesion area...
July 2017: Pain
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