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Adenosine receptor

Mariana Alves, Edward Beamer, Tobias Engel
Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype...
2018: Frontiers in Pharmacology
Rafael V M Manalo, Paul M B Medina
Previous studies have suggested that caffeine reduces the risk of L-DOPA-induced dyskinesia. However, caffeine is also known to promote dopamine signaling, which seemingly contradicts this observed effect. To this end, the study aimed to clarify the mechanism of caffeine neuroprotection in vivo when excess dopamine is present. Transgenic Caenorhabditis elegans (UA57) overproducing dopamine was exposed to caffeine for 7 days and monitored by observing GFP-tagged dopaminergic (DA) neurons via fluorescence microscopy...
2018: Frontiers in Neuroscience
Jie Gao, Jun Li, Wen-Chao Geng, Fang-Yuan Chen, Xingchen Duan, Zhe Zheng, Dan Ding, Dong-Sheng Guo
Activatable phototheranostics is highly appealing to meet the demand of precision medicine. However, although displaying the efficacy in construction of activatable photosensitizers (PSs), direct covalent decoration still shows some inevitable issues, such as complex molecular design, tedious synthesis, possible photoactivity changes and potential toxicity. Herein, we propose a novel concept of biomarker displacement activation (BDA) using host-guest strategy. To exemplify BDA, we engineered a PS-loaded nanocarrier by utilizing a macrocyclic amphiphile, where the fluorescence and photoactivity of PS were completely annihilated by the complexation of macrocyclic receptor (OFF state)...
March 21, 2018: Journal of the American Chemical Society
Skanda Rajasundaram
Our increasing appreciation of adenosine as an endogenous signaling molecule that terminates inflammation has generated excitement regarding the potential to target adenosine receptors (ARs) in the treatment of multiple sclerosis (MS), a disease of chronic neuroinflammation. Of the four G protein-coupled ARs, A2ARs are the principal mediator of adenosine's anti-inflammatory effects and accordingly, there is a growing body of evidence surrounding the role of A2ARs in experimental autoimmune encephalomyelitis (EAE), the dominant animal model of MS...
2018: Frontiers in Immunology
Irena Svobodova, Anirban Bhattaracharya, Milorad Ivetic, Zdenka Bendova, Hana Zemkova
The circadian rhythms in physiological and behavioral functions are driven by a pacemaker located in the suprachiasmatic nucleus (SCN). The rhythms continue in constant darkness and depend on cell-cell communication between neurons and glia. The SCN astrocytes generate also a circadian rhythm in extracellular adenosine 5'-triphosphate (ATP) accumulation, but molecular mechanisms that regulate ATP release are poorly understood. Here, we tested the hypothesis that ATP is released via the plasma membrane purinergic P2X7 receptors (P2X7Rs) and P2Y receptors (P2YRs) which have been previously shown to be expressed in the SCN tissue at transcriptional level...
2018: Frontiers in Pharmacology
Ghulam Hussain, Azhar Rasul, Haseeb Anwar, Nimra Aziz, Aroona Razzaq, Wei Wei, Muhammad Ali, Jiang Li, Xiaomeng Li
Neurodegenerative diseases are conventionally demarcated as disorders with selective loss of neurons. Conventional as well as newer molecules have been tested but they offer just symptomatic advantages along with abundant side effects. The discovery of more compelling molecules that can halt the pathology of these diseases will be considered as a miracle of present time. Several synthetic compounds are available but they may cause several other health issues. Therefore, natural molecules from the plants and other sources are being discovered to replace available medicines...
2018: International Journal of Biological Sciences
Claire Hudson, Tomomi E Kimura, Aparna Duggirala, Graciela B Sala-Newby, Andrew C Newby, Mark Bond
Vascular smooth muscle cell (VSMC) proliferation has been implicated in the development of restenosis after angioplasty, vein graft intimal thickening and atherogenesis. We investigated the mechanisms underlying positive and negative regulation of VSMC proliferation by the transcription factor cyclic AMP response element binding protein (CREB). Incubation with the cAMP elevating stimuli, adenosine, prostacyclin mimetics or low levels of forksolin activated CREB without changing CREB phosphorylation on serine-133 but induced nuclear translocation of the CREB co-factors CRTC-2 and CRTC-3...
March 20, 2018: Scientific Reports
Andreas Weber, Mareike Barth, Jessica Isabel Selig, Silja Raschke, Konstantinos Dakaras, Alexander Hof, Julia Hesse, Jürgen Schrader, Artur Lichtenberg, Payam Akhyari
Calcific aortic valve disease is an active disease process with lipoprotein deposition, chronic inflammation, and progressive leaflet degeneration. Expression of ectonucleotidases, a group of membrane-bound enzymes that regulate the metabolism of ATP and its metabolites, may coregulate the degeneration process of valvular interstitial cells (VICs). The aim of this study was to investigate the role of the enzymes of the purinergic system in the degeneration process of VICs. Ovine VICs were cultivated in vitro under different prodegenerative conditions and treated with inhibitors of ectonucleoside triphosphate diphosphohydrolase 1 (CD39)/ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and 5'-nucleotidase (CD73), as well as with adenosine and adenosine receptor agonists...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Víctor Fernandez-Duenas, Sergi Ferré, Francisco Ciruela
No abstract text is available yet for this article.
February 2018: Neural Regeneration Research
Robert Galinsky, Joanne O Davidson, Justin M Dean, Colin R Green, Laura Bennet, Alistair J Gunn
Perinatal encephalopathy remains a major cause of disability, such as cerebral palsy. Therapeutic hypothermia is now well established to partially reduce risk of disability in late preterm/term infants. However, new and complementary therapeutic targets are needed to further improve outcomes. There is increasing evidence that glia play a key role in neural damage after hypoxia-ischemia and infection/inflammation. In this review, we discuss the role of astrocytic gap junction (connexin) hemichannels in the spread of neural injury after hypoxia-ischemia and/or infection/inflammation...
February 2018: Neural Regeneration Research
Małgorzata Łupina, Maciej Tarnowski, Irena Baranowska-Bosiacka, Sylwia Talarek, Piotr Listos, Jolanta Kotlińska, Izabela Gutowska, Joanna Listos
The present study focused upon the role of SB-334867, an orexin-1 receptor antagonist, in the acquisition of morphine-induced sensitization to locomotor activity in mice. Behavioral sensitization is an enhanced systemic reaction to the same dose of an addictive substance, which assumingly increases both the desire for the drug and the risk of relapse to addiction. Morphine-induced sensitization in mice was achieved by sporadic doses (five injections every 3 days) of morphine (10 mg/kg, i.p.), while a challenge dose of morphine (10 mg/kg) was injected 7 days later...
March 20, 2018: Molecular Neurobiology
Kenneth E Remy, Mark H Yazer, Arun Saini, Ajlana Mehanovic-Varmaz, Sharon R Rogers, Col Andrew P Cap, Philip C Spinella
BACKGROUND: Agitation of platelet units stored at room temperature is performed routinely to maintain platelet function and leukoreduction of blood products is standard of care in many countries to reduce immune consequences of transfusion. The effect of agitation and leukoreduction on whole blood stored at 4° C requires investigation as reductions in hemostatic capacity of whole blood may reduce its efficacy in treating trauma-induced coagulopathy and platelet dysfunction. We hypothesize that agitation of whole blood will not affect hemostatic function and that leukoreduction will reduce hemostatic function of whole blood...
March 16, 2018: Journal of Trauma and Acute Care Surgery
Masanori Tsujimoto, Yukiko Enomoto, Masafumi Miyai, Yusuke Egashira, Toru Iwama
Purpose To determine the best platelet function test for in-stent tissue protrusion following carotid artery stenting (CAS). Methods Patients who underwent CAS were recruited prospectively in this observational study. Combination of aspirin 100 mg/day and clopidogrel 75 mg/day was administered for a minimum of 7 days prior to procedure. Platelet aggregation was measured by light transmittance aggregometry (LTA) following stimulation by adenosine diphosphate (ADP), collagen, and thrombin receptor activating peptide (TRAP) and by the point of care assay, VerifyNow which measures aspirin and thienopyridine reaction units...
January 1, 2018: Journal of International Medical Research
E Ferretti, A L Horenstein, C Canzonetta, F Costa, F Morandi
Adenosine (ADO) is an immunosuppressive molecule with multiple functions in different human organs. ADO is released through the concerted action of surface molecules endowed with enzymatic functions, that belong to two different adenosinergic pathways. The canonical pathway is started by CD39, that converts ATP to AMP. On the other hand, the non-canonical pathway metabolizes NAD+ to ADPR, through the action of CD38. The latter byproduct is then converted to AMP by CD203a/PC-1. Both pathways converge to CD73, that fully degrades AMP to the final product ADO...
March 14, 2018: Immunology Letters
Jesse Lea Carlin, Shalini Jain, Romain Duroux, R Rama Suresh, Cuiying Xiao, John A Auchampach, Kenneth A Jacobson, Oksana Gavrilova, Marc L Reitman
Extracellular adenosine is a danger/injury signal that initiates protective physiology, such as hypothermia. Adenosine has been shown to trigger hypothermia via agonism at A1 and A3 adenosine receptors (A1 AR, A3 AR). Here, we find that adenosine continues to elicit hypothermia in mice null for A1 AR and A3 AR and investigated the effect of agonism at A2A AR or A2B AR. The poorly brain penetrant A2A AR agonists CGS-21680 and PSB-0777 caused hypothermia, which was not seen in mice lacking A2A AR. MRS7352, a likely non-brain penetrant A2A AR antagonist, inhibited PSB-0777 hypothermia...
March 13, 2018: Neuropharmacology
Xiang Song, Yan Zhang, Li Zhang, Wengang Song, Lixin Shi
Hypoxia-associated metabolic reprogramming modulates the biological functions of many immune and non-immune cells, and affects immune response types and intensities. Adenosine and indoleamine 2,3-dioxygenase (IDO) are known immunosuppressors, and adenosine is a hypoxia-associated product. We investigated the impact of hypoxia on IDO production in dendritic cells (DCs). We found that hypoxia (1% O2 ) enhances IDO production in DCs, and this increase was dependent on the adenosine A3 receptor (A3R), but not A2aR or A2bR...
February 20, 2018: Oncotarget
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
Marija Adzic, Nadezda Nedeljkovic
CD73 is a bifunctional glycosylphosphatidylinositol (GPI)-anchored membrane protein which functions as ecto-5'-nucleotidase and a membrane receptor for extracellular matrix protein (ECM). A large body of evidence demonstrates a critical involvement of altered purine metabolism and particularly, increased expression of CD73 in a number of human disorders, including cancer and immunodeficiency. Massive up-regulation of CD73 was also found in reactive astrocytes in several experimental models of human neuropathologies...
2018: Frontiers in Pharmacology
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
Mabrouka Salem, Alain Tremblay, Julie Pelletier, Bernard Robaye, Jean Sévigny
In this study, we investigated the role of extracellular nucleotides in chemokine (KC, MIP-2, MCP-1, and CXCL10) expression and secretion by murine primary intestinal epithelial cells (IECs) with a focus on P2Y6 receptors. qRT-PCR experiments showed that P2Y6 was the dominant nucleotide receptor expressed in mouse IEC. In addition, the P2Y6 ligand UDP induced expression and secretion of CXCL10. For the other studies, we took advantage of mice deficient in P2Y6 ( P2ry6 -/- ). Similar expression levels of P2Y1 , P2Y2 , P2X2, P2X4, and A2A were detected in P2ry6 -/- and WT IEC...
2018: Frontiers in Pharmacology
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