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https://www.readbyqxmd.com/read/29774059/inflammation-in-stroke-the-role-of-cholinergic-purinergic-and-glutamatergic-signaling
#1
REVIEW
Abraham Martín, María Domercq, Carlos Matute
The inflammatory response is a major factor in stroke pathophysiology and contributes to secondary neuronal damage in both acute and chronic stages of the ischemic injury. Recent work in experimental cerebral ischemia has demonstrated the involvement of neurotransmitter signaling in the modulation of neuroinflammation. The present review discusses recent findings on the therapeutic potential and diagnostic perspectives of cholinergic, purinergic and glutamatergic receptors and transporters in experimental stroke...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29769005/adenosine-synthetic-methods-of-its-derivatives-and-antitumor-activity
#2
Margarita Gutierrez, Francisco Valdes, Victor Luna, Barbara Arevalo, Nelson Brown
Since 1929, several researchers have conducted studies in relation the nucleoside of adenosine (1) mainly distribution identifying, characterizing their biological importance and synthetic chemistry to which this type of molecule has been subjected to obtain multiple of its derivatives. The receptors that interact with adenosine and its derivatives, called purinergic receptors, are classified as A1, A2A, A2B and A3. In the presence of agonists and antagonists, these receptors are involved in various physiological processes and diseases...
May 16, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29761007/behavioral-changes-induced-through-adenosine-a2a-receptor-ligands-in-a-rat-depression-model-induced-by-olfactory-bulbectomy
#3
Karla Margarita Padilla, Andres Quintanar-Setephano, Fabian López-Vallejo, Laura Cristina Berumen, Ricardo Miledi, Guadalupe García-Alcocer
Background: Major depressive disorders are characterized by their severity and long-lasting symptoms, which make such disorders highly disabling illnesses. Unfortunately, 50% of major depressive patients experience relapses, perhaps partly because drug research has been performed only in animal models that screen for antidepressant drugs that appear to only ameliorate acute depression symptoms. The bilateral olfactory bulbectomy (OBX) animal model presents the advantage of mimicking the symptoms of chronic depression by means of brain surgery...
May 2018: Brain and Behavior
https://www.readbyqxmd.com/read/29758281/purinergic-molecules-in-the-epidermis
#4
Youichi Ogawa, Manao Kinoshita, Nao Mizumura, Shiho Miyazaki, Rui Aoki, Akira Momosawa, Shinji Shimada, Taiho Kambe, Tatsuyoshi Kawamura
No abstract text is available yet for this article.
May 11, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29758241/targeting-the-cd73-adenosine-axis-in-immuno-oncology
#5
REVIEW
David Allard, Pavel Chrobak, Bertrand Allard, Nouredin Messaoudi, John Stagg
The ectonucleotidases CD39 and CD73 are cell surface enzymes that catabolize the breakdown of extracellular ATP into adenosine. As such, they constitute critical components of the extracellular purinergic pathway and play important roles in maintaining tissue and immune homeostasis. With the coming of age of cancer immunotherapy, ectonucleotidases and adenosine receptors have emerged as novel therapeutic targets to enhance antitumor immune responses. With early-phase clinical trials showing promising results, it is becoming increasingly important to decipher the distinct mechanisms-of-action of adenosine-targeting agents, identify patients that will benefit from these agents and rationally develop novel synergistic combinations...
May 11, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29752814/valproic-acid-inhibits-atp-triggered-ca-2-release-via-a-p38-dependent-mechanism-in-bend-3-endothelial-cells
#6
Iat-Lon Leong, Tien-Yao Tsai, Kar-Lok Wong, Lian-Ru Shiao, Ka-Shun Cheng, Paul Chan, Yuk-Man Leung
Valproic acid (VA) is currently used to treat epilepsy and bipolar disorder. It has also been demonstrated to promote neuroprotection and neurogenesis. Although beneficial actions of VA on brain blood vessels have also been demonstrated, the effects of VA on brain endothelial cell (EC) Ca2+ signaling is hitherto unreported. In this report we examined the effects of VA on agonist-triggered Ca2+ signaling in mouse cortical bEND.3 EC. While VA (100 μM) did not cause an acute inhibition of ATP-triggered Ca2+ signaling, a 30-min VA treatment strongly suppressed ATP-triggered intracellular Ca2+ release; however, such treatment did not affect Ca2+ release triggered by cyclopiazonic acid, an inhibitor of SERCA Ca2+ pump, suggesting there was no reduction in Ca2+ store size...
May 12, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29749377/p2rx7-mapk1-2-sp1-axis-inhibits-mtor-independent-hspb1-mediated-astroglial-autophagy
#7
Ji-Eun Kim, Ah-Reum Ko, Hye-Won Hyun, Su-Ji Min, Tae-Cheon Kang
Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29745882/the-adenosinergic-system-a-potential-player-in-the-pathogenesis-of-anca-associated-vasculitis
#8
REVIEW
Lovis Kling, Bernhard K Krämer, Benito A Yard, Anna-Isabelle Kälsch
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially lethal autoimmune disease whose pathology comprises disturbed T cell differentiation and functionality accompanied by dysfunctional autoreactive immunoglobulin development, culminating in destructive innate immune response as well. Purines, adenine nucleotides and adenosine in particular, have been elucidated as potent extracellular mediators for fine adjustment of these pivotal processes establishing human immunity. Therefore, the extracellular purinergic microenvironment is under control of ectonucleotidases CD39 and CD73 degrading pro-inflammatory adenosine triphosphate (ATP) to anti-inflammatory adenosine as well as adenosine deaminase bound to CD26 deactivating adenosine...
May 3, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29742297/advances-in-cellular-and-integrative-control-of-oxygen-homeostasis-within-the-central-nervous-system
#9
Jan-Marino Ramirez, Liza Severs, Sanja C Ramirez, Ibis M Agosto-Marlin
Mammals must continuously regulate the levels of O2 and CO2 , which is particularly important for the brain. Failure to maintain adequate O2 /CO2 homeostasis has been associated with numerous disorders including sleep apnea, Rett syndrome, and sudden infant death syndrome (SIDS). But, O2 /CO2 homeostasis poses major regulatory challenges, even in the healthy brain. Neuronal activities change in a differentiated, spatially and temporally complex manner, which is reflected in equally complex changes in O2 demand...
May 9, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29739973/impaired-neural-pathway-in-gastric-muscles-of-patients-with-diabetes
#10
Yang Won Min, Eun-Ju Ko, Ji-Yeon Lee, Poong-Lyul Rhee
To explore the pathogenic mechanism of diabetic gastropathy, we investigated differences in response to electrical field stimulation (EFS) of gastric muscles from diabetic and non-diabetic (control) patients. Gastric specimens were obtained from 34 patients and 45 controls who underwent gastrectomy for early gastric cancer. Using organ bath techniques, we examined peak and nadir values of contraction under EFS. To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine, MRS2500, and N-nitro-L-arginine (L-NNA) were added sequentially to the organ bath...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739879/chemical-synapses-without-synaptic-vesicles-purinergic-neurotransmission-through-a-calhm1-channel-mitochondrial-signaling-complex
#11
Roman A Romanov, Robert S Lasher, Brigit High, Logan E Savidge, Adam Lawson, Olga A Rogachevskaja, Haitian Zhao, Vadim V Rogachevsky, Marina F Bystrova, Gleb D Churbanov, Igor Adameyko, Tibor Harkany, Ruibiao Yang, Grahame J Kidd, Philippe Marambaud, John C Kinnamon, Stanislav S Kolesnikov, Thomas E Finger
Conventional chemical synapses in the nervous system involve a presynaptic accumulation of neurotransmitter-containing vesicles, which fuse with the plasma membrane to release neurotransmitters that activate postsynaptic receptors. In taste buds, type II receptor cells do not have conventional synaptic features but nonetheless show regulated release of their afferent neurotransmitter, ATP, through a large-pore, voltage-gated channel, CALHM1. Immunohistochemistry revealed that CALHM1 was localized to points of contact between the receptor cells and sensory nerve fibers...
May 8, 2018: Science Signaling
https://www.readbyqxmd.com/read/29733889/adenosine-promotes-endplate-nachr-channel-activity-in-adult-mouse-skeletal-muscle-fibres-via-low-affinity-p1-receptors
#12
Annalisa Bernareggi, Elisa Ren, Arthur Giniatullin, Elisa Luin, Marina Sciancalepore, Rashid Giniatullin, Paola Lorenzon
Adenosine is a powerful modulator of skeletal neuromuscular transmission, operating via inhibitory or facilitatory purinergic-type P1 receptors. To date, studies have been focused mainly on the effect of adenosine on presynaptic P1 receptors controlling transmitter release. In this study, using two-microelectrode voltage clamp and single channel patch-clamp recording techniques, we have explored potential postsynaptic targets of adenosine and their modulatory effect on nicotinic acetylcholine receptor (nAChR)-mediated synaptic responses in adult mouse skeletal muscle fibres in vitro...
May 4, 2018: Neuroscience
https://www.readbyqxmd.com/read/29731674/electrophysiological-evidence-for-functional-astrocytic-p2x-3-receptors-in-the-mouse-trigeminal-caudal-nucleus
#13
Jaekwang Lee, Jin Young Bae, C Justin Lee, Yong Chul Bae
Recently, we reported that astrocytes in the trigeminal caudal nucleus (Vc) of the brain stem express a purinergic receptor P2X3 , which is involved in the craniofacial pathologic pain. Although we observed protein expression of P2X3 receptors (P2X3 Rs) in the astrocyte of the Vc, it is still unclear that astrocyte has functional P2X3 Rs in Vc. To address this issue, we recorded asrtocytic P2X3 Rs by using whole cell voltage-clamp recording in the Vc of the GFAP-GFP mice, which was used as a guide to astrocytes with green fluorescence...
April 2018: Experimental Neurobiology
https://www.readbyqxmd.com/read/29729039/effects-of-calcium-and-sodium-on-atp-induced-vasopressin-release-from-rat-isolated-neurohypophysial-terminals
#14
E E Custer, T K Knott, S Ortiz-Miranda, J R Lemos
ATP-receptors (P2X2, P2X3, P2X4 & P2X7) are found in neurohypophysial terminals (NHT). These purinergic receptor subtypes are known to be cation selective. Here we confirm that both sodium (Na+ ) and calcium (Ca2+ ) are permeable through these NHT purinergic receptors, but to varying degrees (91% vs. 9%, respectively). Furthermore, extracellular calcium inhibits the ATP-current magnitude. Thus, the objective of this study was to determine the effects of extracellular Na+ vs. Ca2+ on ATP-induced vasopressin (AVP) release from populations of rat isolated NHT...
May 4, 2018: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29725032/novel-evidence-that-extracellular-nucleotides-and-purinergic-signaling-induce-innate-immunity-mediated-mobilization-of-hematopoietic-stem-progenitor-cells
#15
Mateusz Adamiak, Kamila Bujko, Monika Cymer, Monika Plonka, Talita Glaser, Magda Kucia, Janina Ratajczak, Henning Ulrich, Ahmed Abdel-Latif, Mariusz Z Ratajczak
Pharmacological mobilization of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB) is a result of mobilizing agent-induced "sterile inflammation" in the BM microenvironment due to complement cascade (ComC) activation. Here we provide evidence that ATP, as an extracellular nucleotide secreted in a pannexin-1-dependent manner from BM cells, triggers activation of the ComC and initiates the mobilization process. This process is augmented in a P2X7 receptor-dependent manner, and P2X7-KO mice are poor mobilizers...
March 30, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29723720/serum-uric-acid-levels-in-first-episode-mania-effect-on-clinical-presentation-and-treatment-response-data-from-a-case-control-study
#16
Seshadri Sekhar Chatterjee, Sutanuka Ghosal, Sayantanava Mitra, Nitu Mallik, Malay Kumar Ghosal
Bipolar disorder (BD) patients have increased serum Uric Acid (UA) levels as compared to their healthy counterparts. They also demonstrate higher impulsivity - while symptomatic, as well as when in remission. Impulsivity adds a risk of self-harming behavior to BD, and studies show that it increases with UA levels. Given this complex relationship, the current project aimed at comparing UA levels in first-episode mania patients with matched controls, and analyzes its relationship with impulsivity, symptom severity and disease prognosis...
April 26, 2018: Asian Journal of Psychiatry
https://www.readbyqxmd.com/read/29717535/structural-basis-for-nucleotide-recognition-by-the-ectoenzyme-cd203c
#17
Alexei Gorelik, Antsa Randriamihaja, Katalin Illes, Bhushan Nagar
The ecto-nucleotide pyrophosphatase/phosphodiesterase (NPP) enzyme family modulates purinergic signaling by degrading extracellular nucleotides. CD203c (NPP3, ENPP3) regulates the inflammatory response of basophils via ATP hydrolysis and is a marker for allergen sensitivity on the surface of these cells. Multiple other roles and substrates have also been proposed for this protein. In order to gain insight into its molecular functions, we determined the crystal structure of human NPP3 as well as its complex with an ATP analog...
May 2, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29713276/amyotrophic-lateral-sclerosis-als-and-adenosine-receptors
#18
REVIEW
Ana M Sebastião, Nádia Rei, Joaquim A Ribeiro
In the present review we discuss the potential involvement of adenosinergic signaling, in particular the role of adenosine receptors, in amyotrophic lateral sclerosis (ALS). Though the literature on this topic is not abundant, the information so far available on adenosine receptors in animal models of ALS highlights the interest to continue to explore the role of these receptors in this neurodegenerative disease. Indeed, all motor neurons affected in ALS are responsive to adenosine receptor ligands but interestingly, there are alterations in pre-symptomatic or early symptomatic stages that mirror those in advanced disease stages...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29698570/interleukin-2-promotes-hepatic-regulatory-t-cell-responses-and-protects-from-biliary-fibrosis-in-murine-sclerosing-cholangitis
#19
Amy E Taylor, Alexandra N Carey, Ramesh Kudira, Celine S Lages, Tiffany Shi, Simon Lam, Rebekah Karns, Julia Simmons, Kumar Shanmukhappa, Maha Almanan, Claire A Chougnet, Alexander G Miethke
In the Mdr2 -/- mouse model low phospholipid bile instigates biliary epithelial injury, sterile inflammation, and fibrosis, thereby recapitulating disease mechanisms implicated in biliary atresia (BA) and primary sclerosing cholangitis. We hypothesize that T-lymphocytes contribute to the biliary injury and fibrosis in murine sclerosing cholangitis (SC) and that they are susceptible to suppression by regulatory T cells (Tregs). In juvenile Mdr2 -/- mice, intrahepatic CD8 lymphocytes were expanded and contraction of intrahepatic Tregs coincided with rising serum alanine transferase (ALT) and alkaline phosphatase (ALP) levels between days 14-30 of life...
April 26, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29692728/purinergic-receptors-in-neurological-diseases-with-motor-symptoms-targets-for-therapy
#20
REVIEW
Ágatha Oliveira-Giacomelli, Yahaira Naaldijk, Laura Sardá-Arroyo, Maria C B Gonçalves, Juliana Corrêa-Velloso, Micheli M Pillat, Héllio D N de Souza, Henning Ulrich
Since proving adenosine triphosphate (ATP) functions as a neurotransmitter in neuron/glia interactions, the purinergic system has been more intensely studied within the scope of the central nervous system. In neurological disorders with associated motor symptoms, including Parkinson's disease (PD), motor neuron diseases (MND), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's Disease (HD), restless leg syndrome (RLS), and ataxias, alterations in purinergic receptor expression and activity have been noted, indicating a potential role for this system in disease etiology and progression...
2018: Frontiers in Pharmacology
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