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Purinergic signalling review

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https://www.readbyqxmd.com/read/29315226/unfolding-role-of-a-danger-molecule-adenosine-signaling-in-modulation-of-microbial-infection-and-host-cell-response
#1
REVIEW
Jaden S Lee, Özlem Yilmaz
Ectonucleotidases CD39 and CD73, specific nucleotide metabolizing enzymes located on the surface of the host, can convert a pro-inflammatory environment driven by a danger molecule extracellular-ATP to an adenosine-mediated anti-inflammatory milieu. Accordingly, CD39/CD73 signaling have has strongly implicated in modulating the intensity, duration, and composition of purinergic danger signals delivered to host. Recent studies have eluted potential roles for CD39 and CD73 in selective triggering of a variety of host immune cells and molecules in the presence of pathogenic microorganisms or microbial virulence molecules...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29274390/extracellular-atp-signaling-and-clinical-relevance
#2
REVIEW
Lei Dou, Yi-Fa Chen, Peter J Cowan, Xiao-Ping Chen
Since purinergic signaling was discovered in the early 1970s, it has been shown that extracellular nucleotides, and their derivative nucleosides, are released in a regulated or unregulated manner by cells in various challenging settings and then bind defined purinergic receptors to activate intricate signaling networks. Extracellular ATP plays a role based on different P2 receptor subtypes expressed on specific cell types. Sequential hydrolysis of extracellular ATP catalyzed by ectonucleotidases (e.g. CD39, CD73) is the main pathway for the generation of adenosine, which in turn activates P1 receptors...
December 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29249968/purinergic-receptors-in-adipose-tissue-as-potential-targets-in-metabolic-disorders
#3
REVIEW
Marco Tozzi, Ivana Novak
Extracellular nucleosides and nucleotides, such as adenosine and adenosine triphosphate (ATP), are involved in many physiological and pathological processes in adipose tissue (AT). It is becoming accepted that, in addition to the well-established sympathetic and hormonal system, purinergic receptors contribute significantly to regulation of adipocyte functions. Several receptor subtypes for both adenosine (P1) and ATP (P2X and P2Y) have been characterized in white adipocytes (WA) and brown adipocytes (BA). The effects mediated by adenosine and ATP on adipocytes are multiple and often differing, depending on specific receptors activated...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29233884/revisiting-multimodal-activation-and-channel-properties-of-pannexin-1
#4
REVIEW
Yu-Hsin Chiu, Michael S Schappe, Bimal N Desai, Douglas A Bayliss
Pannexin 1 (Panx1) forms plasma membrane ion channels that are widely expressed throughout the body. Panx1 activation results in the release of nucleotides such as adenosine triphosphate and uridine triphosphate. Thus, these channels have been implicated in diverse physiological and pathological functions associated with purinergic signaling, such as apoptotic cell clearance, blood pressure regulation, neuropathic pain, and excitotoxicity. In light of this, substantial attention has been directed to understanding the mechanisms that regulate Panx1 channel expression and activation...
December 12, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29184552/multifaceted-effects-of-extracellular-adenosine-triphosphate-and-adenosine-in-the-tumor-host-interaction-and-therapeutic-perspectives
#5
REVIEW
Paola de Andrade Mello, Robson Coutinho-Silva, Luiz Eduardo Baggio Savio
Cancer is still one of the world's most pressing health-care challenges, leading to a high number of deaths worldwide. Immunotherapy is a new developing therapy that boosts patient's immune system to fight cancer by modifying tumor-immune cells interaction in the tumor microenvironment (TME). Extracellular adenosine triphosphate (eATP) and adenosine (Ado) are signaling molecules released in the TME that act as modulators of both immune and tumor cell responses. Extracellular adenosine triphosphate and Ado activate purinergic type 2 (P2) and type 1 (P1) receptors, respectively, triggering the so-called purinergic signaling...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29120881/atp-and-t-cell-mediated-rejection
#6
Eduardo Castillo-Leon, Sergio Dellepiane, Paolo Fiorina
PURPOSE OF REVIEW: Purine nucleosides and nucleotides are released in the extracellular space following cell injury and act as paracrine mediators through a number of dedicated membrane receptors. In particular, extracellular ATP (eATP) significantly influences T-lymphocyte activation and phenotype. The purpose of this review is to discuss the role of ATP signaling in the T-cell-mediated alloimmune response. RECENT FINDINGS: In various animal models of solid transplantation, the purinergic axis has been targeted to prevent acute rejection and to promote long-term graft tolerance...
November 7, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29018360/adenosine-direct-and-indirect-actions-on-gastric-acid-secretion
#7
REVIEW
Rosa M Arin, Adriana Gorostidi, Hiart Navarro-Imaz, Yuri Rueda, Olatz Fresnedo, Begoña Ochoa
Composed by a molecule of adenine and a molecule of ribose, adenosine is a paradigm of recyclable nucleoside with a multiplicity of functions that occupies a privileged position in the metabolic and regulatory contexts. Adenosine is formed continuously in intracellular and extracellular locations of all tissues. Extracellular adenosine is a signaling molecule, able to modulate a vast range of physiologic responses in many cells and organs, including digestive organs. The adenosine A1, A2A, A2B, and A3 receptors are P1 purinergic receptors, G protein-coupled proteins implicated in tissue protection...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28886985/pannexin-1-channels-in-epilepsy
#8
REVIEW
Mark S Aquilino, Paige Whyte-Fagundes, Georg Zoidl, Peter L Carlen
Pannexin-1 (Panx1) expression is raised in several animal seizure models and in resected human epileptic brain tissue, suggesting relevance to epilepsy. Multiple factors that are characteristic of seizures are thought to regulate Panx1 channel opening, including elevated levels of extracellular K(+). Panx1, when open, 1) releases ATP, glutamate, and other metabolites into the extracellular medium, and 2) may depolarize the membrane due to a channel reversal potential around 0mV. Resultant ATP release from stimulated Panx1 can activate purinergic receptors, including P2X7 receptors...
September 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28870136/ectonucleotidase-inhibitors-a-patent-review-2011-2016
#9
Mariya Al-Rashida, Syeda Uroos Qazi, Nayab Batool, Abdul Hameed, Jamshed Iqbal
Ectonucleotidases are a broad family of metallo-ectoenzymes that are responsible for hydrolysing a variety of nucleotides to nucleosides, hence orchestrating the activation of P1 and P2 cell receptors via controlled release of nucleotides and nucleosides. Many disorders such as impaired calcification including aortic calcification, neurological and immunological disorders, platelet aggregation, cell proliferation and metastasis. are characterized by an increase in expression of these ectonucleotidases. Consequently, selective inhibitors of ectonucleotidases are required for therapeutic intervention...
September 5, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28815512/p2y2-receptor-functions-in-cancer-a-perspective-in-the-context-of-colorectal-cancer
#10
Fernand-Pierre Gendron, Morgane Placet, Guillaume Arguin
Purinergic signaling has recently emerged as a network of signaling molecules, enzymes and receptors that coordinates the action and behavior of cancerous cells. Extracellular adenosine 5' triphosphate activates a plethora of P2 nucleotide receptors that can putatively modulate cancer cell proliferation, survival and dissemination. In this context, the G protein-coupled P2Y2 receptor was identified as one of the entities coordinating the cellular and molecular events that characterize cancerous cells. In this chapter, we will look at the contribution of the P2Y2 receptor in cancer outcomes and use this information to demonstrate that the P2Y2 receptor represents a drug target of interest in the setting of colorectal cancer, for which the role and function of this receptor is poorly defined...
August 17, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28781164/imaging-sympathetic-neurogenic-ca-2-signaling-in-blood-vessels
#11
REVIEW
Withrow Gil Wier, Joseph R H Mauban
We review the information that has been provided by optical imaging experiments directed at understanding the role and effects of sympathetic nerve activity (SNA) in the functioning of blood vessels. Earlier studies utilized electric field stimulation of nerve terminals (EFS) in isolated arteries and vascular tissues (ex vivo) to elicit SNA, but more recently, imaging studies have been conducted in vivo, enabling the study of SNA in truly physiological conditions. Ex vivo: In vascular smooth muscle cells (VSMC) of isolated arteries, the three sympathetic neurotransmitters, norepinephrine (NE), ATP and neuropeptide Y (NPY), elicit or modulate distinct patterns of Ca(2+) signaling, as revealed by confocal imaging of exogenous fluorescent Ca(2+) indicators...
November 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28735873/the-therapeutic-potential-of-purinergic-signalling
#12
REVIEW
Geoffrey Burnstock
This review is focused on the pathophysiology and therapeutic potential of purinergic signalling. A wide range of diseases are considered, including those of the central nervous system, skin, kidney, musculoskeletal, liver gut, lower urinary tract, cardiovascular, airways and reproductive systems, the special senses, infection, diabetes and obesity. Several purinergic drugs are already on the market, including P2Y12 receptor antagonists for stroke and thrombosis, P2Y2 receptor agonists for dry eye, and A1 receptor agonists for supraventricular tachycardia...
July 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28702845/regulation-of-cardiac-ca-2-and-ion-channels-by-shear-mechanotransduction
#13
REVIEW
Joon-Chul Kim, Min-Jeong Son, Jun Wang, Sun-Hee Woo
Cardiac contraction is controlled by a Ca(2+) signaling sequence that includes L-type Ca(2+) current-gated opening of Ca(2+) release channels (ryanodine receptors) in the sarcoplasmic reticulum (SR). Local Ca(2+) signaling in the atrium differs from that in the ventricle because atrial myocytes lack transverse tubules and have more abundant corbular SR. Myocardium is subjected to a variety of forces with each contraction, such as stretch, shear stress, and afterload, and adapts to those mechanical stresses...
July 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28699505/tackling-chronic-pain-and-inflammation-through-the-purinergic-system
#14
Giulia Magni, Daniele Riccio, Stefania Ceruti
The purinergic system is composed of purine and pyrimidine transmitters, of the enzymes that modulate the interconversion of nucleotides and nucleosides, of the membrane transporters that control their extracellular concentrations, and of the many receptor subtypes that are responsible for their cellular responses. The components of this system are ubiquitously localized in all tissues and organs, and their involvement in several physiological conditions has been clearly demonstrated. Moreover, extracellular purine and pyrimidine concentrations raise several folds under pathological conditions like tissue damage, ischemia, and inflammation, which suggest that this signaling system might contribute both to disease outcome and, possibly, to its tentative resolution...
July 10, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28649232/ion-channels-of-pituitary-gonadotrophs-and-their-roles-in-signaling-and-secretion
#15
REVIEW
Stanko S Stojilkovic, Ivana Bjelobaba, Hana Zemkova
Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs) spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28648830/purinergic-p2y-receptors-molecular-diversity-and-implications-for-treatment-of-cardiovascular-diseases
#16
REVIEW
Akiyuki Nishimura, Caroline Sunggip, Sayaka Oda, Takuro Numaga-Tomita, Makoto Tsuda, Motohiro Nishida
Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes...
June 23, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28616712/vesicular-nucleotide-transporter-vnut-appearance-of-an-actress-on-the-stage-of-purinergic-signaling
#17
REVIEW
Yoshinori Moriyama, Miki Hiasa, Shohei Sakamoto, Hiroshi Omote, Masatoshi Nomura
Vesicular storage of ATP is one of the processes initiating purinergic chemical transmission. Although an active transport mechanism was postulated to be involved in the processes, a transporter(s) responsible for the vesicular storage of ATP remained unidentified for some time. In 2008, SLC17A9, the last identified member of the solute carrier 17 type I inorganic phosphate transporter family, was found to encode the vesicular nucleotide transporter (VNUT) that is responsible for the vesicular storage of ATP...
June 14, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28588493/p2x4-receptor-function-in-the-nervous-system-and-current-breakthroughs-in-pharmacology
#18
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/28580666/connexins-and-pannexins-at-the-junction-of-neuro-glial-homeostasis-disease
#19
REVIEW
Andrew S Lapato, Seema K Tiwari-Woodruff
In the central nervous system (CNS), connexin (Cx)s and pannexin (Panx)s are an integral component of homeostatic neuronal excitability and synaptic plasticity. Neuronal Cx gap junctions form electrical synapses across biochemically similar GABAergic networks, allowing rapid and extensive inhibition in response to principle neuron excitation. Glial Cx gap junctions link astrocytes and oligodendrocytes in the pan-glial network that is responsible for removing excitotoxic ions and metabolites. In addition, glial gap junctions help constrain excessive excitatory activity in neurons and facilitate astrocyte Ca(2+) slow wave propagation...
June 5, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28547076/purinergic-signaling-during-intestinal-inflammation
#20
REVIEW
Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang, Simon C Robson
Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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