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Purinergic signalling review

Geoffrey Burnstock
The roles of purinergic signalling in diseases of the central nervous system and the potential use of purinergic compounds for their treatment are attracting increasing attention. In this review, the focus is on the findings reported in recent papers and reviews to update knowledge in this field.
September 22, 2016: CNS & Neurological Disorders Drug Targets
Martin S Minns, Vickery Trinkaus-Randall
Nucleotide release and purinergic signaling make up the earliest response to corneal injury and are vital for proper wound healing. In this study, we review the importance of nucleotide release in the injury response and focus on the contribution of 2 receptors that mediate purinergic signaling, P2Y2 and P2X7. These receptors mediate the early response to injury and activate downstream signaling to promote cytoskeletal rearrangement and cell migration. The contribution of corneal nerves to the purinergic injury response is also discussed...
September 19, 2016: Journal of Ocular Pharmacology and Therapeutics
Amir Pelleg, Edward S Schulman, Peter J Barnes
In recent years, numerous studies have generated data supporting the hypothesis that extracellular adenosine 5'-triphosphate (ATP) plays a major role in obstructive airway diseases. Studies in animal models and human subjects have shown that increased amounts of extracellular ATP are found in the lungs of patients with COPD and asthma and that ATP has effects on multiple cell types in the lungs, resulting in increased inflammation, induction of bronchoconstriction, and cough. These effects of ATP are mediated by cell surface P2 purinergic receptors and involve other endogenous inflammatory agents...
October 2016: Chest
Ana Carolina Morandini, Carlos F Santos, Ӧzlem Yilmaz
Epigenetic mechanisms have rapidly and controversially emerged as silent modulators of host defenses that can lead to a more prominent immune response and shape the course of inflammation in host. Thus, the epigenetics can both drive the production of specific inflammatory mediators and control the magnitude of host response. The epigenetic actions that are predominantly shown to modulate the host defense against microbial pathogens are DNA methylation, histone modification, and the activity of non-coding RNAs...
August 18, 2016: Pathogens and Disease
Kentaro Takezawa, Makoto Kondo, Norio Nonomura, Shoichi Shimada
AIM: Bladder functional disorders are common health problems; however, their pathologies are poorly understood. Adenosine triphosphate (ATP) released from the urothelium has been suggested to have an essential role in the micturition reflex, and its involvement in bladder functional disorders has been intensively investigated. Here, we review the latest advances in research on urothelial ATP signaling. METHODS: We reviewed research articles on the role of the urothelium and urothelial ATP release in bladder function...
August 19, 2016: Neurourology and Urodynamics
Lauren C Strazzulla, Bruce N Cronstein
There is growing recognition that bone serves important endocrine and immunologic functions that are compromised in several disease states. While many factors are known to affect bone metabolism, recent attention has focused on investigating the role of purinergic signaling in bone formation and regulation. Adenosine is a purine nucleoside produced intracellularly and extracellularly in response to stimuli such as hypoxia and inflammation, which then interacts with P1 receptors. Numerous studies have suggested that these receptors play a pivotal role in osteoblast, osteoclast, and chondrocyte differentiation and function...
July 29, 2016: Purinergic Signalling
Aitziber Buqué, Norma Bloy, Fernando Aranda, Isabelle Cremer, Alexander Eggermont, Wolf Hervé Fridman, Jitka Fucikova, Jérôme Galon, Radek Spisek, Eric Tartour, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Progressing malignancies establish robust immunosuppressive networks that operate both systemically and locally. In particular, as tumors escape immunosurveillance, they recruit increasing amounts of myeloid and lymphoid cells that exert pronounced immunosuppressive effects. These cells not only prevent the natural recognition of growing neoplasms by the immune system, but also inhibit anticancer immune responses elicited by chemo-, radio- and immuno therapeutic interventions. Throughout the past decade, multiple strategies have been devised to counteract the accumulation or activation of tumor-infiltrating immunosuppressive cells for therapeutic purposes...
June 2016: Oncoimmunology
Robin R Hodges, Darlene A Dartt
PURPOSE: Purinergic receptors play a key role in the function of the lacrimal gland (LG) as P1 purinergic receptors A1, A2A, and A2B, P2X1-7 receptors, and many of the P2Y receptors are expressed. METHODS: This review examines the current knowledge of purinergic receptors in the LG as well as the signaling pathways activated by these receptors. RESULTS: These receptors are expressed on the acinar, ductal, and myoepithelial cells. Considerable crosstalk exists between the pathways activated by P2X7 receptors with those activated by M3 muscarinic or α1D adrenergic receptors...
October 2016: Journal of Ocular Pharmacology and Therapeutics
Erica F Diezmos, Paul P Bertrand, Lu Liu
Purinergic receptors play an important role in inflammation, and can be activated by ATP released via pannexin channels and/or connexin hemichannels. The purinergic P2X7 receptor (P2X7R) is of interest since it is involved in apoptosis when activated. Most studies focus on the influence of pannexin-1 (Panx1) and connexin 43 (Cx43) on ATP release and how it affects P2X7R function during inflammation. Inflammatory bowel disease (IBD) is characterized by uncontrolled inflammation within the gastrointestinal system...
2016: Frontiers in Neuroscience
Lin-Hua Jiang, Yunjie Hao, Fatema Mousawi, Hongsen Peng, Xuebin Yang
Extracellular ATP and other nucleotides induce autocrine and/or paracrine purinergic signalling via activation of the P2 receptors on the cell surface, which represents one of the most common signalling mechanisms. Mesenchymal stem cells (MSC) are a type of multipotent adult stem cells that have many promising applications in regenerative medicine. There is increasing evidence to show that extracellular nucleotides regulate MSC functions and P2 receptor-mediated purinergic signalling plays an important role in such functional regulation...
July 12, 2016: Journal of Cellular Physiology
Valentina Di Liberto, Giuseppa Mudò, Roberta Garozzo, Monica Frinchi, Víctor Fernandez-Dueñas, Patrizia Di Iorio, Renata Ciccarelli, Francesco Caciagli, Daniele F Condorelli, Francisco Ciruela, Natale Belluardo
Guanine-based purines (GBPs) have been recently proposed to be not only metabolic agents but also extracellular signaling molecules that regulate important functions in the central nervous system. In such way, GBPs-mediated neuroprotection, behavioral responses and neuronal plasticity have been broadly described in the literature. However, while a number of these functions (i.e., GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown...
2016: Frontiers in Pharmacology
Makoto Tsuda
Neuropathic pain is a debilitating chronic pain and represents a major clinical challenge. The molecular and cellular mechanisms underlying its development and maintenance are not fully understood but involve abnormal excitability in the dorsal horn of the spinal cord. A growing body of evidence has shown that this aberrant excitability may be a consequence not merely of changes in neurons but rather of multiple alterations in microglia, which are resident macrophages in the central nervous system. This review highlights recent advances in our understanding of the mechanisms that underlie neuropathic pain caused by peripheral nerve injury, with a specific focus on purinergic signaling in spinal cord microglia...
July 4, 2016: Journal of Neuroscience Research
Yong Tang, Hai-Yan Yin, Patrizia Rubini, Peter Illes
Chronic pain is a debilitating and rather common health problem. The present shortage in analgesic drugs with a favorable spectrum but without remarkable side effects furthered the search for alternative therapeutic manipulations. Increasing evidence from both basic and clinical research on acupuncture, a main alternative therapy of traditional Chinese medicine, suggests that chronic pain is sensitive to acupuncture procedures. Clarification of the underlying mechanisms is a challenge of great theoretical and practical significance...
June 25, 2016: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Julie C Lim, Ankita Umapathy, Angus C Grey, Ehsan Vaghefi, Paul J Donaldson
Outside the traditional roles of the lens as an important refractive element and a UV filter, it was David Beebe's group that first demonstrated that the lens acts an oxygen sink that protects the tissues of the anterior segment of the eye from oxygen or oxygen metabolites. In this review, we follow on from this work and present new evidence from our laboratory to demonstrate that the lens serves as a reservoir for the release of the antioxidant glutathione (GSH) into the aqueous humor to provide a source of GSH and/or its precursor amino acids to nearby tissues that interface with the aqueous humor, or to remove toxic metabolites from the eye via the aqueous outflow pathway...
June 6, 2016: Experimental Eye Research
Leigh Anne Swayne, Steffany A L Bennett
Connexins and pannexins share very similar structures and functions; they also exhibit overlapping expression in many stages of neuronal development. Here, we review evidence implicating connexin- and pannexin-mediated communication in the regulation of the birth and development of neurons, specifically Cx26, Cx30, Cx32, Cx36, Cx43, Cx45, Panx1, and Panx2. We begin by dissecting the involvement of these proteins in the generation and development of new neurons in the embryonic, postnatal, and adult brain. Next we briefly outline common mechanisms employed by both pannexins and connexins in these roles, including modulation of purinergic receptor signalling and signalling nexus functions...
2016: BMC Cell Biology
Carola Ledderose, Yi Bao, Yutaka Kondo, Mahtab Fakhari, Christian Slubowski, Jingping Zhang, Wolfgang G Junger
PURPOSE: Sepsis remains an unresolved clinical problem with high in-hospital mortality. Despite intensive research over decades, no treatments for sepsis have become available. Here we explore the role of ATP in the pathophysiology of sepsis. ATP is not only a universal energy carrier but it also acts as an extracellular signaling molecule that regulates immune function. ATP stimulates a large family of purinergic receptors found on the cell surface of virtually all mammalian cells. In severe sepsis and septic shock, ATP is released in large amounts into the extracellular space where it acts as a "danger" signal...
May 2016: Clinical Therapeutics
Davide Ferrari, Eóin N McNamee, Marco Idzko, Roberto Gambari, Holger K Eltzschig
Migration and positioning of immune cells is fundamental for their differentiation and recruitment at sites of infection. Besides the fundamental role played by chemokines and their receptors, recent studies demonstrate that a complex network of purinergic signaling events plays a key role in these trafficking events. This process includes the release of nucleotides (such as ATP and ADP) and subsequent autocrine and paracrine signaling events through nucleotide receptors. At the same time, surface-expressed ectoapyrases and nucleotidases convert extracellular nucleotides to adenosine, and adenosine signaling events play additional functional roles in leucocyte trafficking...
June 2016: Trends in Immunology
Zar Chi Thent, Chiranjib Chakraborty, Pasuk Mahakkanukrauh, Nik Kosai, Reynu Rajan, Srijit Das
Recently, there are scientific attempts to devise new drugs in the biotechnology industry in order to treat various diseases including atherosclerosis. Atherosclerosis is considered to be a leading cause of death throughout the world. Atherosclerosis involves oxidative damage to the cells with production of reactive oxygen species (ROS). Development of atheromatous plaques in the arterial wall is a common feature. Specific inflammatory markers pertaining to the arterial wall in atherosclerosis may be useful for both diagnosis and treatment...
May 2, 2016: Current Drug Targets
R Zeiser, S C Robson, T Vaikunthanathan, M Dworak, G Burnstock
Purinergic signaling has been recognized to play an important role in inflammation, angiogenesis, malignancy, diabetes and neural transmission. Activation of signaling pathways downstream of purinergic receptors may also be implicated in transplantation and related vascular injury. Following transplantation, the pro-inflammatory "danger signal" adenosine triphosphate (ATP) is released from damaged cells and promotes proliferation and activation of a variety of immune cells. Targeting purinergic signaling pathways may promote immunosuppression and ameliorate inflammation...
March 23, 2016: American Journal of Transplantation
Elham Safarzadeh, Farhad Jadidi-Niaragh, Morteza Motallebnezhad, Mehdi Yousefi
INTRODUCTION: Multiple sclerosis (MS) is a heterogeneous neurological disorder with multifactorial etiologies characterized by demyelination, axonal degeneration, and oligodendroglial death. It is believed that both genetics and environmental risk factors such as infection are involved in disease etiology. Accumulating evidence indicates that alteration in purinergic system signaling is involved in immunity and inflammation. Adenosine, a key purine nucleoside, has been shown to be produced during metabolic stress, including ischemia, inflammatory condition, and tissue injury...
July 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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