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adenosine receptors

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https://www.readbyqxmd.com/read/30333323/coordination-of-ent2-dependent-adenosine-transport-and-signaling-dampens-mucosal-inflammation
#1
Carol M Aherne, Colm B Collins, Caroline R Rapp, Kristine E Olli, Loni Perrenoud, Paul Jedlicka, Jessica L Bowser, Tingting W Mills, Harry Karmouty-Quintana, Michael R Blackburn, Holger K Eltzschig
Intestinal epithelial barrier repair is vital for remission in inflammatory bowel disease (IBD). Extracellular adenosine signaling has been implicated in promoting restoration of epithelial barrier function. Currently, no clinically approved agents target this pathway. Adenosine signaling is terminated by uptake from the extracellular space via equilibrative nucleoside transporters (ENTs). We hypothesized that ENT inhibition could dampen intestinal inflammation. Initial studies demonstrated transcriptional repression of ENT1 and ENT2 in IBD biopsies or in murine IBD models...
October 18, 2018: JCI Insight
https://www.readbyqxmd.com/read/30326239/characterisation-of-the-mechanisms-underlying-the-special-sensitivity-of-the-ca2-hippocampal-area-to-adenosine-receptor-antagonists
#2
María-Dolores Muñoz, José M Solís
Recent studies have underscored the importance of the CA2 area in social memory formation. This area, a narrow transition zone between hippocampal CA3 and CA1 areas, is endowed with special connectivity and a distinctive molecular composition. In particular, adenosine A1 receptors (A1 R) are enriched in CA2, and based on the prominent synaptic potentiation induced by A1 R antagonists (e.g., caffeine) in this area, it has been proposed that CA2 is under the strong tonic control of A1 R activation. It is unclear whether this special sensitivity of CA2 to A1 R antagonists is due to an elevated extracellular concentration of adenosine or to a different A1 R function...
October 13, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30324870/oral-antiplatelet-agents-in-cardiovascular-disease
#3
Joseph Pultar, Patricia P Wadowski, Simon Panzer, Thomas Gremmel
Antiplatelet agents significantly reduce mortality and morbidity in ischemic heart disease, cerebrovascular disease and peripheral artery disease (PAD), and are therefore part of guideline-driven daily medical treatment in these patients. Due to its beneficial effects in the secondary prevention of atherothrombotic events, aspirin remains the most frequently prescribed antiplatelet agent in cardiovascular disease. In patients with acute coronary syndromes (ACS) and in those undergoing angioplasty with stent implantation dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor antagonist is indicated...
October 16, 2018: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/30323284/synthetic-cadpr-analogues-may-form-only-one-of-two-possible-conformational-diastereoisomers
#4
Joanna M Watt, Mark P Thomas, Barry V L Potter
Cyclic adenosine 5'-diphosphate ribose (cADPR) is an emerging Ca2+ -mobilising second messenger. cADPR analogues have been generated as chemical biology tools via both chemo-enzymatic and total synthetic routes. Both routes rely on the cyclisation of a linear precursor to close an 18-membered macrocyclic ring. We show here that, after cyclisation, there are two possible macrocyclic product conformers that may be formed, depending on whether cyclisation occurs to the "right" or the "left" of the adenine base (as viewed along the H-8 → C-8 base axis)...
October 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30323244/irisin-inhibits-pancreatic-cancer-cell-growth-via-the-ampk-mtor-pathway
#5
Jiayu Liu, Nannan Song, Yibing Huang, Yuxin Chen
Irisin, a recently identified myokine that is released from skeletal muscle following exercise, regulates body weight and influences various metabolic diseases such as obesity and diabetes. In this study, human recombinant nonglycosylated P-irisin (expressed in Escherichia coli prokaryote cell system) or glycosylated E-irisin (expressed in Pichia pastoris eukaryote cell system) were compared to examine the role of recombinant irisin against pancreatic cancer (PC) cells lines, MIA PaCa-2 and Panc03.27. MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-di phenyltetrazolium bromide] and cell colony formation assays revealed that irisin significantly inhibited the growth of MIA PaCa-2 and Panc03...
October 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30322034/role-of-extracellular-loops-and-membrane-lipids-for-ligand-recognition-in-the-neuronal-adenosine-receptor-type-2a-an-enhanced-sampling-simulation-study
#6
Ruyin Cao, Alejandro Giorgetti, Andreas Bauer, Bernd Neumaier, Giulia Rossetti, Paolo Carloni
Human G-protein coupled receptors (GPCRs) are important targets for pharmaceutical intervention against neurological diseases. Here, we use molecular simulation to investigate the key step in ligand recognition governed by the extracellular domains in the neuronal adenosine receptor type 2A (hA2A R), a target for neuroprotective compounds. The ligand is the high-affinity antagonist (4-(2-(7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-ylamino)ethyl)phenol), embedded in a neuronal membrane mimic environment...
October 12, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/30320355/synergistic-effects-of-vemurafenib-and-fingolimod-fty720-in-vemurafenib%C3%A2-resistant-melanoma-cell-lines
#7
Tomoko Takahashi, Naoko Abe, Hiroyuki Kanoh, Yoshiko Banno, Mariko Seishima
Vemurafenib, a selective inhibitor of mutated BRAF, is used to treat late‑stage melanoma. However, resistance to vemurafenib is urgently required as it can have fatal consequences. Fingolimod (FTY720), a sphingosine‑1‑phosphate receptor modulator, has been used for the treatment of several malignant neoplasms in clinical trials. The present study investigated the effects of FTY720 and vemurafenib combination treatment on cell death induction, and defined the molecular mechanisms in vemurafenib‑resistant melanoma cells...
October 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30320335/lithocarpus-polystachyus-rehd-leaves-aqueous-extract-protects-against-hydrogen-peroxide%C3%A2-induced-sh-sy5y-cells-injury-through-activation-of-sirt3-signaling-pathway
#8
Jianmei Gao, Yingshu Xu, Jianyong Zhang, Jingshan Shi, Qihai Gong
Lithocarpus polystachyus Rehd. (sweet tea; ST) leaves is a type of Chinese folkloric medicine from southern China. The purpose of the present study was to explore the neuroprotective effect of ST, and to explore its underlying mechanisms in hydrogen peroxide (H2O2)‑induced neuronal cell injury in cultured human neuroblastoma. H2O2 was used as oxidant inducer and human SH‑SY5Y neuroblastoma cells were treated with various concentrations of ST. Cell viability and cell death were detected using MTT and LDH assays, respectively...
October 5, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/30319359/activation-of-astrocytic-%C3%AE-opioid-receptor-elicits-fast-glutamate-release-through-trek-1-containing-k2p-channel-in-hippocampal-astrocytes
#9
Dong Ho Woo, Jin Young Bae, Min-Ho Nam, Heeyoung An, Yeon Ha Ju, Joungha Won, Jae Hyouk Choi, Eun Mi Hwang, Kyung-Seok Han, Yong Chul Bae, C Justin Lee
Recently, μ-opioid receptor (MOR), one of the well-known Gi-protein coupled receptors (Gi-GPCR), was reported to be highly expressed in the hippocampal astrocytes. However, the role of astrocytic MOR has not been investigated. Here we report that activation of astrocytic MOR by [D-Ala2 ,N-MePhe4 ,Gly-ol]-enkephalin (DAMGO), a selective MOR agonist, causes a fast glutamate release using sniffer patch technique. We also found that the DAMGO-induced glutamate release was not observed in the astrocytes from MOR-deficient mice and MOR-short hairpin RNA (shRNA)-expressed astrocytes...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/30319280/identification-of-key-gene-pathways-and-coexpression-networks-of-islets-in-human-type-2-diabetes
#10
Lu Li, Zongfu Pan, Si Yang, Wenya Shan, Yanyan Yang
Purpose: The number of people with type 2 diabetes (T2D) is growing rapidly worldwide. Islet β-cell dysfunction and failure are the main causes of T2D pathological processes. The aim of this study was to elucidate the underlying pathways and coexpression networks in T2D islets. Materials and methods: We analyzed the differentially expressed genes (DEGs) in the data set GSE41762, which contained 57 nondiabetic and 20 diabetic samples, and developed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/30319131/-sequencing-and-combination-of-agents-in-castration-resistant-prostate-cancer
#11
Ana Victoria Ojeda, María José Ledo, José Luís Alvarez-Ossorio
Prostate Cancer is the second most frequent malignant neoplasm in males in the world. At the end of the disease, when the tumor becomes resistant to castration, we have a wide range of treatment possibilities aimed at the Androgenic Receptor, androgens synthesis, the skeleton, chemotherapy, and even new molecular targets that are still under investigation. Today, the best sequence of treatment for each patient has not been established yet. OBJECTIVE: The objective of this work is to review the current scene of treatment in castrate resistant prostate cancer, as well as the latest developments and strategies to choose the best sequence in each patient...
September 2018: Archivos Españoles de Urología
https://www.readbyqxmd.com/read/30318008/adenosine-as-a-marker-and-mediator-of-cardiovascular-homeostasis-a-translational-perspective
#12
Trevor Simard, Richard Jung, Alisha Labinaz, Mohammad Ali Faraz, F Daniel Ramirez, Pietro Di Santo, Ian Pitcher, Pouya Motazedian, Chantal Gaudet, Rebecca Rochman, Jeffrey Marbach, Paul Boland, Kiran Sarathy, Saleh Alghofaili, Juan J Russo, Etienne Couture, Robert S Beanlands, Benjamin Hibbert
Adenosine, a purine nucleoside, is produced broadly and implicated in the homeostasis of many cells and tissues. It signals predominantly via 4 purinergic adenosine receptors (ADORs) - ADORA1, ADORA2A, ADORA2B and ADORA3 in addition to non-ADOR mediated effects. Through these signaling mechanisms, adenosine exerts effects on numerous cell types crucial to maintaining vascular homeostasis, especially following vascular injury. Both in vitro and in vivo models have provided considerable insights into adenosine signaling and identified targets for therapeutic intervention...
October 10, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/30315630/adenosine-a-1-receptor-mrna-expression-by-neurons-and-glia-in-the-auditory-forebrain
#13
Troy A Hackett
In the brain, purines such as ATP and adenosine can function as neurotransmitters and co-transmitters, or serve as signals in neuron-glial interactions. In thalamocortical (TC) projections to sensory cortex, adenosine functions as a negative regulator of glutamate release via activation of the presynaptic adenosine A1 receptor (A1 R). In the auditory forebrain, restriction of A1 R-adenosine signaling in medial geniculate (MG) neurons is sufficient to extend LTP, LTD, and tonotopic map plasticity in adult mice for months beyond the critical period...
October 12, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/30310263/activator-protein-1-contributes-to-the-nacl-induced-expression-of-vegf-and-plgf-in-rpe-cells
#14
Jana Kleiner, Margrit Hollborn, Peter Wiedemann, Andreas Bringmann
Purpose: Systemic hypertension is a risk factor of neovascular age-related macular degeneration; consumption of dietary salt resulting in extracellular hyperosmolarity is a main cause of hypertension. Extracellular hyperosmolarity was shown to induce expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), in RPE cells. The aim of the present study was to determine whether the hyperosmotic expression of growth factor genes in RPE cells is mediated by activator protein-1 (AP-1), and whether c-Fos and c-Jun genes are regulated by extracellular osmolarity...
2018: Molecular Vision
https://www.readbyqxmd.com/read/30309298/decidualization-of-human-endometrial-stromal-fibroblasts-is-a-multiphasic-process-involving-distinct-transcriptional-programs
#15
Kalle T Rytkönen, Eric M Erkenbrack, Matti Poutanen, Laura L Elo, Mihaela Pavlicev, Günter P Wagner
Decidual stromal cells differentiate from endometrial stromal fibroblasts (ESFs) under the influence of progesterone and cyclic adenosine monophosphate (cAMP) and are essential for implantation and the maintenance of pregnancy. They evolved in the stem lineage of placental (eutherian) mammals coincidental with the evolution of implantation. Here we use the well-established in vitro decidualization protocol to compare early (3 days) and late (8 days) gene transcription patterns in immortalized human ESF. We document extensive, dynamic changes in the early and late decidual cell transcriptomes...
October 11, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/30308941/identification-of-alkaloids-from-corydalis-yanhusuo-w-t-wang-as-dopamine-d%C3%A2-receptor-antagonists-by-using-cre-luciferase-reporter-gene-assay
#16
Lehao Wu, Weiyue Zhang, Xin Qiu, Chaoran Wang, Yanfang Liu, Zhiwei Wang, Yang Yu, Richard D Ye, Yan Zhang
Corydalis yanhusuo W. T. Wang ( C. yanhusuo ) has been traditionally used for drug addiction and pain relief in China. In our previous study, we showed that the extract of C. yanhusuo blocks dopamine receptors, demonstrating that its pharmacological activities are mostly due to the antagonistic effects of some of its components at dopamine receptors. As part of our ongoing project on C. yanhusuo , the aim of the present study is to establish a high-throughput and low-cost screening assay system and test the abilities of the isolated alkaloids from C...
October 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/30307561/inhibiting-adenosine-receptor-signaling-promotes-accumulation-of-effector-cd4-t-cells-in-the-lung-parenchyma-during-severe-tuberculosis
#17
Eduardo Pinheiro Amaral, Érika Machado de Salles, Caio Cesar Barbosa Bomfim, Rafael Moysés Salgado, Fabrício M Almeida, Paula Carolina de Souza, José Maria Alvarez, Mario H Hirata, Elena B Lasunskaia, Maria Regina D'Império-Lima
Background: Tuberculous pneumonia, necrotic granulomatous lesions, and bacterial dissemination characterize severe forms of mycobacterial infection. Methods: To evaluate the pulmonary CD4+ T-cell response during severe tuberculosis, C57BL/6 mice were infected with approximately 100 bacilli of 3 hypervirulent mycobacterial isolates (Mycobacterium tuberculosis strain Beijing 1471 and Mycobacterium bovis strains B2 and MP287/03) or the H37Rv M tuberculosis strain as reference for mycobacterial virulence...
October 11, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/30304995/oxidative-stress-impairs-fatty-acid-oxidation-and-mitochondrial-function-in-the-term-placenta
#18
Megan M Thomas, Maricela Haghiac, Catalin Grozav, Judi Minium, Virtu Calabuig-Navarro, Perrie O'Tierney-Ginn
Placental fatty acid oxidation (FAO) is impaired and lipid storage is increased in pregnancy states associated with chronic oxidative stress. The effect of acute oxidative stress, as seen in pregnancies complicated with asthma, on placental lipid metabolism is unknown. We hypothesized that induction of acute oxidative stress would decrease FAO and increase esterification. We assessed [3 H]-palmitate oxidation and esterification in term placental explants from lean women after exposure to hydrogen peroxide (H2 O2 ) for 4 hours...
October 10, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/30303493/an-update-on-tolvaptan-for-autosomal-dominant-polycystic-kidney-disease
#19
E Poch, L Rodas, M Blasco, A Molina, L Quintana
Tolvaptan is an orally active antagonist of vasopressin (antidiuretic hormone [ADH]) V2 receptors. By blocking water reabsorption in kidney collecting ducts, it prompts renal free-water excretion and has been used for the treatment of hyponatremia, both euvolemic due to the syndrome of inappropriate ADH secretion, and hypervolemic due to liver cirrhosis and congestive heart failure. In the past few years, it has been shown that vasopressin and its second messenger cyclic adenosine monophosphate (cAMP) play an important role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD)...
September 2018: Drugs of Today
https://www.readbyqxmd.com/read/30302410/xanthine-scaffold-scope-and-potential-in-drug-development
#20
REVIEW
Nivedita Singh, Ashwinee Kumar Shreshtha, M S Thakur, Sanjukta Patra
Medicinal plants have been the basis for discovery of various important marketed drugs. Xanthine is one such lead molecule. Xanthines in various forms (caffeine, theophylline, theobromine, etc) are abode in tea, coffee, cocoa, chocolate etc. giving them popular recognition. These compounds are best known for their diverse pharmaceutical applications as cyclic nucleotide phosphodiesterase inhibition, antagonization of adenosine receptor, anti-inflammatory, anti-microbial, anti-oxidant and anti-tumor activities...
October 2018: Heliyon
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