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Purinergic signalling review

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https://www.readbyqxmd.com/read/28886985/pannexin-1-channels-in-epilepsy
#1
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
#2
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
#3
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
#4
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...
July 29, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28735873/the-therapeutic-potential-of-purinergic-signalling
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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"
https://www.readbyqxmd.com/read/28434079/cell-culture-complications-due-to-mechanical-release-of-atp-and-activation-of-purinoceptors
#14
REVIEW
Geoffrey Burnstock, Gillian E Knight
There is abundant evidence that ATP (adenosine 5'-triphosphate) is released from a variety of cultured cells in response to mechanical stimulation. The release mechanism involved appears to be a combination of vesicular exocytosis and connexin and pannexin hemichannels. Purinergic receptors on cultured cells mediate both short-term purinergic signalling of secretion and long-term (trophic) signalling such as proliferation, migration, differentiation and apoptosis. We aim in this review to bring to the attention of non-purinergic researchers using tissue culture that the release of ATP in response to mechanical stress evoked by the unavoidable movement of the cells acting on functional purinergic receptors on the culture cells is likely to complicate the interpretation of their data...
April 22, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28339693/neuronal-signaling-repertoire-in-the-mammalian-sperm-functionality
#15
Alfredo Ramírez-Reveco, Franz Villarroel-Espíndola, Joan E Rodríguez-Gil, Ilona I Concha
The common embryonic origin has been a recurrent explanation to understand the presence of "neural receptors" in sperm. However, this designation has conditioned a bias marked by the classical neurotransmission model, dismissing the possibility that neurotransmitters can play specific roles in the sperm function by themselves. For instance, the launching of acrosome reaction, a fundamental sperm function, includes several steps that recall the process of presynaptic secretion. Unlike of postsynaptic neuron, whose activation is mediated by molecular interaction between neurotransmitter and postsynaptic receptors, the oocyte activation is not mediated by receptors, but by cytosolic translocation of sperm phospholipase (PLCζ)...
March 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28300322/astroglia-as-a-cellular-target-for-neuroprotection-and-treatment-of-neuro-psychiatric-disorders
#16
REVIEW
Beihui Liu, Anja G Teschemacher, Sergey Kasparov
Astrocytes are key homeostatic cells of the central nervous system. They cooperate with neurons at several levels, including ion and water homeostasis, chemical signal transmission, blood flow regulation, immune and oxidative stress defense, supply of metabolites and neurogenesis. Astroglia is also important for viability and maturation of stem-cell derived neurons. Neurons critically depend on intrinsic protective and supportive properties of astrocytes. Conversely, all forms of pathogenic stimuli which disturb astrocytic functions compromise neuronal functionality and viability...
August 2017: Glia
https://www.readbyqxmd.com/read/28284836/exciting-and-not-so-exciting-roles-of-pannexins
#17
REVIEW
Eliana Scemes, Jana Velíšková
It is the current view that purinergic signaling regulates many physiological functions. Pannexin1 (Panx1), a member of the gap junction family of proteins is an ATP releasing channel that plays important physio-pathological roles in various tissues, including the CNS. Upon binding to purinergic receptors expressed in neural cells, ATP triggers cellular responses including increased cell proliferation, cell morphology changes, release of cytokines, and regulation of neuronal excitability via release of glutamate, GABA and ATP itself...
March 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28223127/multidrug-resistance-in-glioblastoma-stem-like-cells-role-of-the-hypoxic-microenvironment-and-adenosine-signaling
#18
REVIEW
Daniel Uribe, Ángelo Torres, José Dellis Rocha, Ignacio Niechi, Carlos Oyarzún, Luis Sobrevia, Rody San Martín, Claudia Quezada
Glioblastoma multiforme (GBM) is considered the most common and aggressive tumour of the central nervous system and is characterized for being highly chemoresistant. This property is mainly due to the activation of Multiple Drug Resistance (MDR) mechanisms that protect cancer cells from structurally and morphologically different drugs. Overexpression and increased ABC transporters activity is one of the most important MDR mechanisms at the clinical level, and both its expression and activity are elevated in GBM cells...
February 20, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28210205/the-atp-gated-p2x7-receptor-as-a-target-for-the-treatment-of-drug-resistant-epilepsy
#19
REVIEW
Edward Beamer, Wolfgang Fischer, Tobias Engel
Despite the progress made in the development of new antiepileptic drugs (AEDs), the biggest challenges that epilepsy presents to drug development have remained unchanged for the last 80 years: finding a treatment with potential for modifying disease progression and reducing the percentage of patients resistant to all pharmacological interventions. The mechanism of action of the majority of AEDs is based on blocking Na(+) and/or Ca(2+) channels, promotion of GABA or inhibition of glutamate signaling. In order for further progress to be made, however, a fuller picture of epilepsy will need to be considered, including changes to blood-brain barrier permeability, synaptic plasticity, network reorganization, and gliosis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28179257/interplay-between-renal-endothelin-and-purinergic-signaling-systems
#20
Eman Y Gohar, Malgorzata Kasztan, David M Pollock
Alterations in extracellular fluid volume regulation and sodium balance may result in the development and maintenance of salt-dependent hypertension, a major risk factor for cardiovascular disease. Numerous pathways contribute to the regulation of sodium excretion and blood pressure, including endothelin and purinergic signaling. Increasing evidence suggests a link between purinergic receptor activation and endothelin production within the renal collecting duct as a means of promoting natriuresis. A better understanding of the relationship between these two systems, especially in regard to sodium homeostasis, will fill a significant knowledge gap and may provide novel antihypertensive treatment options...
February 8, 2017: American Journal of Physiology. Renal Physiology
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