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adenosine receptors

Mohammad Keyvanloo Shahrestanaki, Fatemeh Panahi Arasi, Mahmoud Aghaei
Signaling through A2a adenosine receptor specifically prevent pancreatic β-cells (PBCs) loses under diabetogenic conditions. However, signaling mediators of this receptor in PBCs remained unidentified. Thus, we aimed to investigate the possible involvement of PKA/Akt/IPP-1/CREB pathway in MIN6 β-cells. In addition, we investigated IPP-1 role in A2a receptor signaling pathway. The expression of A2a receptor in MIN6 cell line was evaluated by RT-PCR and its functionality confirmed by quantification of cAMP in response to the CGS 21680, an A2a receptor agonist...
February 14, 2019: European Journal of Pharmacology
Shipin Zhang, Kristeen Ye Wen Teo, Shang Jiunn Chuah, Ruenn Chai Lai, Sai Kiang Lim, Wei Seong Toh
The efficacy of mesenchymal stem cell (MSC) therapies is increasingly attributed to paracrine secretion, particularly exosomes. In this study, we investigated the role of MSC exosomes in the regulation of inflammatory response, nociceptive behaviour, and condylar cartilage and subchondral bone healing in an immunocompetent rat model of temporomandibular joint osteoarthritis (TMJ-OA). We observed that exosome-mediated repair of osteoarthritic TMJs was characterized by early suppression of pain and degeneration with reduced inflammation, followed by sustained proliferation and gradual improvements in matrix expression and subchondral bone architecture, leading to overall joint restoration and regeneration...
February 8, 2019: Biomaterials
Manish Shukla, Koustav Roy, Charanjeet Kaur, Devasharma Nayak, K V Mani, Sangeeta Shukla, Neeru Kapoor
Hearing loss and cognitive decline are commonly associated with aging and morbidity. Present clinical interest lies in whether peripheral hearing loss promotes cognitive decline and if prophylaxis with selective adenosine receptor agonist CGS21680 effectively mitigates the adverse effects. In the current study, male Sprague Dawley rats weighing 200-250 gm were randomly allocated into three groups: Group 1) rats exposed to 100 dB SPL white noise, 2 hours a day for 15 consecutive days, 2) rats supplemented with an adenosine receptor agonist, CGS21680 at 100 μg/kg/day prior to noise exposure and 3) unexposed control rats...
February 13, 2019: Brain Research Bulletin
Byron Miyazawa, Alpa Trivedi, Padma Priya Togarrati, Daniel Potter, Gyulnar Baimukanova, Lindsay Vivona, Maximillian Lin, Ernesto Lopez, Rachael Callcut, Amit K Srivastava, Lucy Z Kornblith, Alexander T Fields, Martin A Schreiber, Charles E Wade, John B Holcomb, Shibani Pati
BACKGROUND: Platelet (Plt) derived-extracellular vesicles (Plt-EVs) have hemostatic properties similar to Plts. In addition to hemostasis, Plts also function to stabilize the vasculature and maintain endothelial cell (EC) barrier integrity. We hypothesized that Plt-EVs would inhibit vascular endothelial cell permeability, similar to fresh Plts. To investigate this hypothesis we utilized in vitro and in vivo models of vascular endothelial compromise and bleeding. METHODS: In vitro: Plt-EVs were isolated by ultracentrifugation and characterized for Plt markers and particle size distribution...
February 13, 2019: Journal of Trauma and Acute Care Surgery
Pierre Guillet, Florian Mahler, Kelly Garnier, Gildas Nyame Mendendy Boussambe, Sébastien Igonet, Carolyn Vargas, Christine Ebel, Marine Soulié, Sandro Keller, Anass Jawhari, Grégory Durand
We report herein the design and synthesis of a novel series of alkyl glycosides detergents consisting of a nonionic polar headgroup that comprises two glucose moieties in a branched arrangement (DG), onto which octane-, decane- and dodecanethiols were grafted leading to ODG, DDG, and DDDG detergents. Micellization in aqueous solution was studied by isothermal titration calorimetry (ITC), 1H NMR spectroscopy, and surface tensiometry (SFT). Critical micellar concentration values were found to decrease by a factor of ~10 for each pair of methylene groups added to the alkyl chain, ranging from ~0...
February 15, 2019: Langmuir: the ACS Journal of Surfaces and Colloids
Sukhi Singh, Tor Damén, Mikael Dellborg, Anders Jeppsson, Andreas Nygren
BACKGROUND: New approaches to prevent bleeding complications during cardiac surgery are needed. OBJECTIVE: To investigate if noradrenaline (NA) enhances platelet aggregation in CABG patients. PATIENTS/METHODS: Twenty-four CABG patients were included in a prospective parallel-group randomized study. All patients but one, were treated with acetylsalicylic acid (ASA). In the treatment group (n=12), mean arterial blood pressure (MAP) was maintained at pre-induction levels by NA infusion...
February 14, 2019: Journal of Thrombosis and Haemostasis: JTH
Isabella Massimi, Laura Alemanno, Maria Luisa Guarino, Raffaella Guerriero, Massimo Mancone, Andrea Ceccacci, Luigi Frati, Dominick J Angiolillo, Fabio M Pulcinelli
Chronic treatment with aspirin in healthy volunteers (HVs) is associated with recovery of adenosine diphosphate (ADP)-induced platelet activation. The purinergic P2Y1 receptor exerts its effects via a Gq -protein, which is the same biochemical pathway activated by thromboxane-A2 receptor. We hypothesized that recovery of ADP-induced platelet activation could be attributed to increased P2Y1 expression induced by chronic aspirin exposure. We performed a multi-phase investigation which embraced both in vitro and in vivo experiments conducted in (1) human megakaryoblastic DAMI cells, (2) human megakaryocytic progenitor cell cultures, (3) platelets obtained from HVs treated with aspirin and (4) platelets obtained from aspirin-treated patients...
February 13, 2019: Thrombosis and Haemostasis
Maria E Yurgel, Priyanka Kakad, Meet Zandawala, Dick R Nässel, Tanja A Godenschwege, Alex C Keene
Dysregulation of sleep and feeding has widespread health consequences. Despite extensive epidemiological evidence for interactions between sleep and metabolic function, little is known about the neural or molecular basis underlying the integration of these processes. D. melanogaster potently suppress sleep in response to starvation, and powerful genetic tools allow for mechanistic investigation of sleep-metabolism interactions. We have previously identified neurons expressing the neuropeptide leucokinin (Lk) as being required for starvation-mediated changes in sleep...
February 13, 2019: PLoS Biology
Monica Armida, Alessandra Matteucci, Antonella Pèzzola, Younis Baqi, Christa E Müller, Patrizia Popoli, Rosa Luisa Potenza
Amyotrophic lateral sclerosis (ALS) is a fatal progressing neurodegenerative disease; to date, despite the intense research effort, only two therapeutic options, with very limited effects, are available. The purinergic system has been indicated as a possible new therapeutic target for ALS, but the results are often contradictory and generally confused. The present study was designed to determine whether P1 adenosine receptor ligands affected disease progression in a transgenic model of ALS. SOD1G93A mice were chronically treated, from presymptomatic stage, with a selective adenosine A2A receptor agonist (CGS21680), antagonist (KW6002) or the A1 receptor antagonist DPCPX...
February 12, 2019: Neurochemical Research
Chiachen Chen, Mary Beth Breslin, Jessie J Guidry, Michael S Lan
Insulinoma associated-1 (INSM1) is a key protein functioning as a transcriptional repressor in neuroendocrine differentiation and is activated by N-Myc in human neuroblastoma (NB). INSM1 modulates the phosphoinositide 3-kinase (PI3K)-AKT Ser/Thr kinase (AKT)-glycogen synthase kinase 3β (GSK3β) signaling pathway through a positive-feedback loop, resulting in N-Myc stabilization. Accordingly, INSM1 has emerged as a critical player closely associated with N-Myc in facilitating NB cell growth. Here, an INSM1 promoter-driven luciferase-based screen revealed that the compound 5'-iodotubercidin suppresses adenosine kinase (ADK), an energy pathway enzyme, and also INSM1 expression and NB tumor growth...
February 12, 2019: Journal of Biological Chemistry
Stoyan Dimitrov, Tanja Lange, Cécile Gouttefangeas, Anja T R Jensen, Michael Szczepanski, Jannik Lehnnolz, Surjo Soekadar, Hans-Georg Rammensee, Jan Born, Luciana Besedovsky
Efficient T cell responses require the firm adhesion of T cells to their targets, e.g., virus-infected cells, which depends on T cell receptor (TCR)-mediated activation of β2 -integrins. Gαs -coupled receptor agonists are known to have immunosuppressive effects, but their impact on TCR-mediated integrin activation is unknown. Using multimers of peptide major histocompatibility complex molecules (pMHC) and of ICAM-1-the ligand of β2 -integrins-we show that the Gαs -coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E2 , PGD2 , and adenosine strongly inhibit integrin activation on human CMV- and EBV-specific CD8+ T cells in a dose-dependent manner...
February 12, 2019: Journal of Experimental Medicine
Hong-Chun Xiang, Li-Xue Lin, Xue-Fei Hu, He Zhu, Hong-Ping Li, Ru-Yue Zhang, Liang Hu, Wen-Tao Liu, Yi-Lin Zhao, Yang Shu, Hui-Lin Pan, Man Li
BACKGROUND: Chronic pain is a major clinical problem with limited treatment options. Previous studies have demonstrated that activation of adenosine monophosphate-activated protein kinase (AMPK) can attenuate neuropathic pain. Inflammation/immune response at the site of complete Freund's adjuvant (CFA) injection is known to be a critical trigger of the pathological changes that produce inflammatory pain. However, whether activation of AMPK produces an analgesic effect through inhibiting the proinflammatory cytokines, including interleukin-1β (IL-1β), in inflammatory pain remains unknown...
February 12, 2019: Journal of Neuroinflammation
Martin Berger, David R J Lutz, Julia Lutz, Jawad S Khalil, Ahmed Aburima, Khalid M Naseem, Francisco Rivero
Typical Rho GTPases, such as Rac1, Cdc42, and RhoA, act as molecular switches regulating various aspects of platelet cytoskeleton reorganization. The loss of these enzymes results in reduced platelet functionality. Atypical Rho GTPases of the RhoBTB subfamily are characterized by divergent domain architecture. One family member, RhoBTB3, is expressed in platelets, but its function is unclear. In the present study we examined the role of RhoBTB3 in platelet function using a knockout mouse model. We found the platelet count, size, numbers of both alpha and dense granules, and surface receptor profile in these mice were comparable to wild-type mice...
February 11, 2019: Cells
Taylor A Gentile, Steven J Simmons, Christopher S Tallarida, Shu Su, Slava Rom, Mia N Watson, Allen B Reitz, Raghava Potula, Scott M Rawls
BACKGROUND AND PURPOSE: Purinergic P2X7 receptors are present on neurons, astrocytes and microglia and activated by extracellular ATP. Since P2X7 receptor activation releases endogenous substrates (e.g., pro-inflammatory cytokines, dopamine, and glutamate) that facilitate psychostimulant reward and reinforcement, we investigated the hypothesis that the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) produces rewarding effects that are dependent on active P2X7 receptors. METHODS: Reward function was measured in male mice using intracranial self-stimulation (ICSS)...
January 31, 2019: Drug and Alcohol Dependence
Deborah Allouche-Fitoussi, Danit Bakhshi, Haim Breitbart
To fertilize the egg, sperm cells must reside in the female reproductive tract for several hours during which they undergo chemical and motility changes collectively called capacitation. During capacitation, the sperm develop a unique type of motility known as hyperactivated motility (HAM). The semen contains Zn2+ in millimolar concentrations, whereas in the female reproductive tract the concentration is around 1 µM. In this study, we characterize the role of Zn 2+ in human sperm capacitation focusing on its effect on HAM...
February 11, 2019: Molecular Reproduction and Development
Maria A Battistone, Maria Merkulova, Yoo-Jin Park, Maria A Peralta, Flavia Gombar, Dennis Brown, Sylvie Breton
KEY POINTS: In the epididymis, elaborate communication networks between epithelial cells are important to establish an optimal acidic luminal environment for the maturation and storage of spermatozoa, which is essential for male fertility. Proton secretion by epididymal clear cells is achieved via the proton pumping V-ATPase located in their apical membrane. Here, we dissect the molecular mechanisms by which clear cells respond to luminal ATP and adenosine to modulate their acidifying activity via the adenosine receptor ADORA2B and the pH-sensitive ATP receptor P2 × 4...
February 12, 2019: Journal of Physiology
Bernadeta Chyrchel, Anna Drożdż, Dorota Długosz, Ewa Ł Stępień, Andrzej Surdacki
Background : Platelet-derived microvesicles (PMVs), shed from platelet surface membranes, constitute the majority of circulating microvesicles and have been implicated in procoagulant, pro-inflammatory and pro-atherosclerotic effects. Our aim was to compare plasma PMVs numbers in relation to platelet reactivity during dual antiplatelet therapy (DAPT) with various P2Y12 adenosine diphosphate (ADP) receptor antagonists. Methods: In pre-discharge men treated with DAPT for an acute coronary syndrome, plasma PMVs were quantified by flow cytometry on the basis of CD62P (P-selectin) and CD42 (glycoprotein Ib) positivity, putative indices of PMVs release from activated and all platelets, respectively...
2019: International Journal of Medical Sciences
Mark H Lewis, Christopher Primiani, Amber M Muehlmann
Repetitive behaviors are seemingly purposeless patterns of behavior that vary little in form and are characteristic of many neurodevelopmental, psychiatric, and neurological disorders. Our work has identified that hypofunctioning of the indirect basal ganglia pathway is associated with the expression of repetitive behavior in the deer mouse model. In this study, we targeted indirect pathway cells of the striatum with single drugs and drug combinations that bind to dopamine D2, adenosine A2A, and glutamate mGlu5 receptors...
February 11, 2019: Journal of Pharmacology and Experimental Therapeutics
Ingrid M Quintana, Johannes Gibhardt, Asan Turdiev, Elke Hammer, Fabian M Commichau, Vincent T Lee, Christian Magni, Jörg Stülke
Cyclic di-adenosine monophosphate (c-di-AMP) is a second messenger involved in diverse metabolic processes including osmolyte uptake, cell wall homeostasis, as well as antibiotic and heat resistance. In Lactococcus lactis , a lactic acid bacterium which is used in the dairy industry and as a cell factory in biotechnological processes, the only reported interaction partners of c-di-AMP are the pyruvate carboxylase and BusR, the transcription regulator of the busAB operon for glycine betaine uptake. However, recent studies uncovered a major role of c-di-AMP in the control of potassium homeostasis, and potassium as the signal that triggers c-di-AMP synthesis...
February 11, 2019: Journal of Bacteriology
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