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Xu Wang, Deyu Chen
Purinergic signaling, which utilizes nucleotides (particularly ATP) and adenosine as transmitter molecules, plays an essential role in immune system. In the extracellular compartment, ATP predominantly functions as a pro-inflammatory molecule through activation of P2 receptors, whereas adenosine mostly functions as an anti-inflammatory molecule through activation of P1 receptors. Neutrophils are the most abundant immune cells in circulation and have emerged as an important component in orchestrating a complex series of events during inflammation...
2018: Frontiers in Immunology
Marta Martínez-Calle, Bárbara Olmeda, Paul Dietl, Manfred Frick, Jesús Pérez-Gil
The release of pulmonary surfactant by alveolar type II (ATII) cells is essential for lowering surface tension at the respiratory air-liquid interface, stabilizing the lungs against physical forces tending to alveolar collapse. Hydrophobic surfactant protein (SP)-B ensures the proper packing of newly synthesized surfactant particles, promotes the formation of the surface active film at the alveolar air-liquid interface and maintains its proper structure along the respiratory dynamics. We report that membrane-associated SP-B efficiently induces secretion of pulmonary surfactant by ATII cells, at the same level as potent secretagogues such as ATP...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Caitlin A Wotton, Elizabeth F Quon, Ashley C Palmer, Lane K Bekar
Both serotonin (5HT) and stress exert changes in cortical inhibitory tone to shape activity of cortical networks. As astrocytes are also known to affect inhibition through established purinergic pathways, we assessed the role of GABA and purinergic pathways in rapid corticosterone (CORT) and 5HT effects on cortical inhibition. We used a paired-pulse paradigm (P1 & P2) in acutely isolated mouse brain slices to evaluate changes in cortical evoked inhibition. Normally, 5HT decreases amplitude of the first pulse P1, while increasing the amplitude of P2 (increase frequency transmission)...
March 15, 2018: Journal of Neuroendocrinology
A M Rodrigues, R S Serralha, C Farias, G R Punaro, M J S Fernandes, Elisa Mieko Suemitsu Higa
Diabetes mellitus is characterized by increased levels of reactive oxygen species (ROS), leading to high levels of adenosine triphosphate (ATP) and the activation of purinergic receptors (P2X7 ), which results in cell death. Klotho was recently described as a modulator of oxidative stress and as having anti-apoptotic properties, among others. However, the roles of P2X7 and klotho in the progression of diabetic nephropathy are still unclear. In this context, the aim of the present study was to characterize P2X7 and klotho in several stages of diabetes in rats...
March 14, 2018: Purinergic Signalling
Ivana Novak, Anna Solini
Type 2 diabetes is reaching an alarming prevalence worldwide. Its complex pathogenesis certainly includes a pivotal role of low-grade inflammation, which could be triggered by excessive purinergic signaling. In this complex scenario, extracellular ATP impairs the function of two key players: β-cell and adipose tissue. In the former, P2Y and possibly some P2X receptors-ion channels regulate insulin secretion, but it is still debated whether excessive ATP can via P2X receptors impair β-cell function directly or whether cell damage is due to an excessive systemic release of cytokines...
March 6, 2018: Current Opinion in Immunology
Colin A Nurse, Erin M Leonard, Shaima Salman
Mammalian carotid bodies (CB) are chemosensory organs that mediate compensatory cardiorespiratory reflexes in response to low blood PO2 (hypoxemia) and elevated CO2 /H+ (acid hypercapnia). The chemoreceptors are glomus or type I cells which occur in clusters enveloped by neighboring glial-like type II cells. During chemoexcitation type I cells depolarize, leading to Ca2+ -dependent release of several neurotransmitters, some excitatory and others inhibitory, which help shape the afferent carotid sinus nerve (CSN) discharge...
March 9, 2018: Physiological Genomics
N-N Song, H-L Lu, C Lu, L Tong, S-Q Huang, X Huang, J Chen, Y-C Kim, W-X Xu
BACKGROUND: A major complication related to gastrointestinal (GI) symptoms in diabetic patients is chronic constipation. Constipation has serious negative impacts on quality of life; however, without a comprehensive understanding of the disease, currently available treatments cannot provide a cure. Platelet-derived growth factor receptor alpha-positive cells (PDGFRα+ cells), which form the SIP syncytium with interstitial cells of Cajal and smooth muscle cells, play important roles in GI motility...
March 9, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Hye Min Lim, Woon Heo, Jung Woo Han, Min Goo Lee, Joo Young Kim
The movement of microglia is regulated mainly by P1 and P2 purinergic receptors, which are activated by various nucleotides and their metabolites. Recently, such purinergic signalling has been spotlighted because of potential roles in the pathophysiologies of neurodegenerative and neuropsychiatric disorders. To understand the characteristics of microglia in relation of P1 and P2 signalling, we investigated the ectoenzymes expressed in microglia. At first, we profiled the expression of all known ectoenzymes in cultured microglia...
March 7, 2018: Purinergic Signalling
José R Lemos, Edward E Custer, Sonia Ortiz-Miranda
Many different types of purinergic receptors are present in the Hypothalamic-Neurohypophysial System (HNS), which synthesizes and releases vasopressin and oxytocin. The specific location of purinergic receptor subtypes has important functional repercussions for neuronal activity and synaptic output. Yet, until the advent of receptor KOs, this had been hindered by the low selectivity of the available pharmacological tools. The HNS offers an excellent opportunity to differentiate the functional properties of these purinergic receptors in cell bodies vs...
March 7, 2018: Journal of Neuroendocrinology
Shilpa Sharma, Ravi Shankar Akundi
BACKGROUND: Depression is a widespread phenomenon with varying degrees of pathology in different patients. Various hypotheses have been proposed for the cause and continuance of depression. Some of these include, but not limited to, the monoamine hypothesis, the neuroendocrine hypothesis, and the more recent epigenetic and inflammatory hypotheses. OBJECTIVE: In this article, we review all the above hypotheses with a focus on the role of mitochondria as the connecting link...
March 2, 2018: Current Neuropharmacology
Carolina Paredes, Shuo Li, Xiaoli Chen, Claudio Coddou
Paralichthys olivaceus P2X7 receptor (poP2X7R) is a recently identified as a P2X7 purinergic receptor involved in innate immunity of the Japanese flounder Paralichthys olivaceus . Divalent metals are allosteric modulators of mammalian P2XRs, but there is no information for fish P2XRs. Here, we characterized the effects of divalent metals on poP2X7R channel activity by electrophysiology and molecular biology techniques. Copper, zinc and mercury inhibited poP2X7R-mediated currents with different maximal inhibition potency, while cadmium had no effect on poP2X7R activity...
March 2018: FEBS Open Bio
Wei Zhang, Biao Zhong, Chi Zhang, Congfeng Luo, Yulin Zhan
Inflammatory cytokines commonly initiate extreme changes in the synovium and cartilage microenvironment of osteoarthritis (OA) patients, which subsequently cause cellular dysfunction, especially in chondrocytes. It has been reported that induction of the purinergic P2X7 receptor (P2X7R) can regulate the expression of a variety of inflammatory factors, including interleukin (IL)-6 and -8, leading to OA pathogenesis. However, knowledge of the mechanism of upregulation of P2X7R in OA is still incomplete, and its role in chondrocyte proliferation is also not clear...
March 2018: FEBS Open Bio
Mandy Juarez, Alejandro Schcolnik-Cabrera, Alfonso Dueñas-Gonzalez
Drug repositioning is a highly studied alternative strategy to discover and develop anticancer drugs. This drug development approach identifies new indications for existing compounds. Ivermectin belongs to the group of avermectins (AVM), a series of 16-membered macrocyclic lactone compounds discovered in 1967, and FDA-approved for human use in 1987. It has been used by millions of people around the world exhibiting a wide margin of clinical safety. In this review, we summarize the in vitro and in vivo evidences demonstrating that ivermectin exerts antitumor effects in different types of cancer...
2018: American Journal of Cancer Research
G Kauffenstein, G G Yegutkin, S Khiati, V Pomozi, O Le Saux, G Leftheriotis, G Lenaers, D Henrion, L Martin
Pseudoxanthoma elasticum (PXE) is a rare genetic condition primarily caused by hepatic ABCC6 transporter dysfunction. Most clinical manifestations of PXE are due to premature calcification of elastic fibers. However, the vascular impact of PXE is pleiotropic and remains ill-defined. ABCC6 expression has recently been associated with cellular nucleotide export. We studied the impact of ABCC6 deficiency on blood levels of adenosine triphosphate (ATP) and related metabolites and on soluble nucleotidase activities in PXE patients and Abcc6-/- mice...
February 28, 2018: Journal of Investigative Dermatology
Sheraz Khoja, Nhat Huynh, Alicia M P Warnecke, Liana Asatryan, Michael W Jakowec, Daryl L Davies
The deleterious effects of alcohol use disorders (AUDs) on human health have been documented worldwide. The enormous socioeconomic burden coupled with lack of efficacious pharmacotherapies underlies the need for improved treatment strategies. At present, there is a growing body of preclinical evidence that demonstrates the potential of avermectins [ivermectin (IVM), selamectin (SEL), abamectin (ABM), and moxidectin (MOX)] in treatment of AUDs. Avermectins are derived by fermentation of soil micro-organism, Streptomyces avermitilis, and have been extensively used for treatment of parasitic infections...
March 2, 2018: Psychopharmacology
Sayuri Suzuki, Annette Lis, Carsten Schmitz, Reinhold Penner, Andrea Fleig
The melastatin-related transient receptor potential member 7 (TRPM7) is a unique fusion protein with both ion channel function and enzymatic α-kinase activity. TRPM7 is essential for cellular systemic magnesium homeostasis and early embryogenesis; it promotes calcium transport during global brain ischemia and emerges as a key player in cancer growth. TRPM7 channels are negatively regulated through G-protein-coupled receptor-stimulation, either by reducing cellular cyclic adenosine monophosphate (cAMP) or depleting phosphatidylinositol bisphosphate (PIP2 ) levels in the plasma membrane...
March 2, 2018: Cellular and Molecular Life Sciences: CMLS
Zhili Rao, Feng Xu, Taoqun Wen, Feng Wang, Wentao Sang, Nan Zeng
The essential oils from Rimulus cinnamon (EORC) have anti-inflammation activities, but the effects of EORC on endotoxin poisoning mice remain to be explored, the mechanism is still unclear. This study was designed to investigate the protective effects and mechanism of EORC on lipopolysaccharide (LPS)-induced endotoxin poisoning mice. Pre-treatment with EORC decreased the production of pro-inflammatory cytokines (Interleukin-1β, Interleukin-18, Interleukin-5, and Interferon-γ) and chemokines (Monocyte chemotactic protein-1, Macrophage colony-stimulating factor, and Macrophage inflammatory protein-1β) in serum of endotoxin poisoning mice...
February 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Noriyuki Hatano, Susumu Ohya, Yuji Imaizumi, Robert B Clark, Darrell Belke, Wayne R Giles
KEY POINTS: Fibroblasts isolated from adult rat ventricles consistently respond to (5-100 μM) ATP. ATP, ADP, and UTP all elicit similar dose-dependent increases in [Ca2+ ]i . ATP also activates an outwardly rectifying Cl- current; in contrast, ADP and UTP have much smaller electrophysiological effects. This ATP-dependent Cl- current is markedly reduced when: i) [Ca2+ ]i is buffered with BAPTA, or ii) the intrinsic phospholipase C activity in these fibroblasts is inhibited. PCR analysis suggests that the ATP-induced current is generated by the Ca2+ -activated Cl- current transcript TMEM 16F, also denoted ANO6...
March 1, 2018: Experimental Physiology
Mirza Muhammad Fahd Qadir, Silvia Álvarez-Cubela, Dagmar Klein, Giacomo Lanzoni, Carlos García-Santana, Abelardo Montalvo, Fabiola Pláceres-Uray, Emilia Maria Cristina Mazza, Camillo Ricordi, Luca Alessandro Inverardi, Ricardo Luis Pastori, Juan Domínguez-Bendala
Treatment of human pancreatic non-endocrine tissue with Bone Morphogenetic Protein 7 (BMP-7) leads to the formation of glucose-responsive β-like cells. Here, we show that BMP-7 acts on extrainsular cells expressing PDX1 and the BMP receptor activin-like kinase 3 (ALK3/BMPR1A). In vitro lineage tracing indicates that ALK3+ cell populations are multipotent. PDX1+ /ALK3+ cells are absent from islets but prominently represented in the major pancreatic ducts and pancreatic duct glands. We identified the purinergic receptor P2Y1 (P2RY1) as a surrogate surface marker for PDX1...
February 27, 2018: Cell Reports
Nishkantha Arulkumaran, Marije L Sixma, Sean Pollen, Elias Ceravola, Elisa Jentho, Maria Prendecki, Paul S Bass, Frederick W K Tam, Robert J Unwin, Mervyn Singer
Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP-sensitive P2X7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluid-resuscitated rat model of fecal peritonitis and acute kidney injury (AKI) to investigate the contribution of this purinergic receptor to renal dysfunction in sepsis. Six and 24 h time-points were chosen to represent early and established sepsis, respectively. A selective P2X7 receptor antagonist (A-438079) dissolved in dimethyl sulfoxide (DMSO) was infused 2 h following induction of sepsis...
March 2018: Physiological Reports
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