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Adenosine receptor

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https://www.readbyqxmd.com/read/29775678/synaptic-transmission-and-excitability-during-hypoxia-with-inflammation-and-reoxygenation-in-hippocampal-ca1-neurons
#1
Yoon-Sil Yang, Sook Jin Son, Joon Ho Choi, Jong-Cheol Rah
Although a number of experimental and clinical studies have shown that hypoxia typically accompanies acute inflammatory responses, the combinatorial effect of the two insults on basic neural function has not been thoroughly investigated. Previous studies have predominantly suggested that hypoxia reduces network activity; however, several studies suggest the opposite effect. Of note, inflammation is known to increase neural activity. In the current study, we examined the effects of limited oxygen in combination with an inflammatory stimulus, as well as the effects of reoxygenation, on synaptic transmission and excitability...
May 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29774115/an-improved-method-for-culturing-patient-derived-colorectal-cancer-spheroids
#2
Hiroyuki Miyoshi, Hisatsugu Maekawa, Fumihiko Kakizaki, Tadayoshi Yamaura, Kenji Kawada, Yoshiharu Sakai, M Mark Taketo
Recent advances allowed culturing and examination of patient-derived colorectal cancer (PD-CRC) cells as organoids or spheroids. To be applied to practical personalized medicine, however, current methods still need to be strengthened for higher efficiency. Here we report an improved method to propagate PD-CRC tumor initiating cells (TICs) in spheroid culture. We established > 100 cancer spheroid lines derived from independent colorectal cancer patients employing a serum-containing medium with additional inhibitors, Y27632 and SB431542...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29772805/ethyl-acetate-fraction-from-persimmon-diospyros-kaki-ameliorates-cerebral-neuronal-loss-and-cognitive-deficit-via-the-jnk-akt-pathway-in-tmt-induced-mice
#3
Jong Min Kim, Seon Kyeong Park, Jin Yong Kang, Su Bin Park, Seul Ki Yoo, Hye Ju Han, Chul-Woo Kim, Uk Lee, Sea-Hyun Kim, Ho Jin Heo
This study was conducted to assess the antioxidant capacity and protective effect of the ethyl acetate fraction from persimmon ( Diospyros kaki ) (EFDK) on H₂O₂-induced hippocampal HT22 cells and trimethyltin chloride (TMT)-induced Institute of Cancer Research (ICR) mice. EFDK had high antioxidant activities and neuroprotective effects in HT22 cells. EFDK ameliorated behavioral and memory deficits in Y-maze, passive avoidance and Morris water maze tests. Also, EFDK restored the antioxidant system by regulating malondialdehyde (MDA), superoxide dismutase (SOD) and reduced gluthathione (GSH), and the cholinergic system by controlling the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity and expression...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29771938/ability-of-%C3%AE-%C3%AE-t-cells-to-modulate-the-foxp3-t-cell-response-is-dependent-on-adenosine
#4
Dongchun Liang, Jeong-Im Woo, Hui Shao, Willi K Born, Rebecca L O'Brien, Henry J Kaplan, Deming Sun
Whether γδ T cells inhibit or enhance the Foxp3 T cell response depends upon their activation status. The critical enhancing effector in the supernatant is adenosine. Activated γδ T cells express adenosine receptors at high levels, which enables them to deprive Foxp3+ T cells of adenosine, and to inhibit their expansion. Meanwhile, cell-free supernatants of γδ T cell cultures enhance Foxp3 T cell expansion. Thus, inhibition and enhancement by γδ T cells of Foxp3 T cell response are a reflection of the balance between adenosine production and absorption by γδ T cells...
2018: PloS One
https://www.readbyqxmd.com/read/29771006/the-anti-fibrotic-effect-of-adenosine-a2b-receptor-antagonism-in-a-mouse-model-of-dermal-fibrosis
#5
Harry Karmouty-Quintana, Jose G Molina, Kemly Philip, Chiara Bellocchi, Brent Gudenkauf, Minghua Wu, Ning-Yuan Chen, Scott D Collum, Junsuk Ko, Sandeep K Agarwal, Shervin Assassi, Hongyan Zhong, Michael R Blackburn, Tingting Weng
OBJECTIVE: Systemic sclerosis (SSc - scleroderma) is a chronic disease that affects the skin and various internal organs. Dermal fibrosis is a major component of this disease. The mechanisms that promote dermal fibrosis remain elusive. Elevations in tissue adenosine levels and the subsequent engagement of the pro-fibrotic A2B adenosine receptor (ADORA2B) have been shown to regulate fibrosis in multiple organs including the lung, kidney and penis; however, the role of the ADORA2B in dermal fibrosis has not been investigated...
May 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29770956/dynamic-changes-of-astrocytes-and-adenosine-signaling-in-rat-hippocampus-in-post-status-epilepticus-model-of-epileptogenesis
#6
Siqi Hong, Tingsong Li, Yuanyuan Luo, Wenjuan Li, Xiaoju Tang, Yuanzhen Ye, Peng Wu, Qiao Hu, Li Cheng, Hengsheng Chen, Li Jiang
It is of great importance to explore the development of epileptogenesis, and the adenosine and adenosine kinase (ADK) system seems to play a key role in this process. The aim of this study is to explore the dynamic changes of astrocytes and adenosine signaling during epileptogenesis in rat hippocampus in a post-status epileptogenesis (SE) model. Rat SE models were built and killed for experiments at 1 day (acute phase of epileptogenesis), 5 days (latent phase), 4 weeks (chronic phase), and 8 weeks (late chronic phase of epileptogenesis) after SE induction...
May 16, 2018: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29770921/neuronal-adenosine-a-2a-receptor-overexpression-is-neuroprotective-towards-3-nitropropionic-acid-induced-striatal-toxicity-a-rat-model-of-huntington-s-disease
#7
Maria Rosaria Domenici, Valentina Chiodi, Mirko Averna, Monica Armida, Antonella Pèzzola, Rita Pepponi, Antonella Ferrante, Michael Bader, Kjell Fuxe, Patrizia Popoli
The A2A adenosine receptor (A2A R) is widely distributed on different cellular types in the brain, where it exerts a broad spectrum of pathophysiological functions, and for which a role in different neurodegenerative diseases has been hypothesized or demonstrated. To investigate the role of neuronal A2A Rs in neurodegeneration, we evaluated in vitro and in vivo the effect of the neurotoxin 3-nitropropionic acid (3-NP) in a transgenic rat strain overexpressing A2A Rs under the control of the neural-specific enolase promoter (NSEA2A rats)...
May 16, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29769837/the-role-of-extracellular-adenosine-generation-in-the-development-of-autoimmune-diseases
#8
REVIEW
F Morandi, A L Horenstein, R Rizzo, F Malavasi
Adenosine (ADO) is an immunosuppressive molecule, which suppresses the immune responses by interacting with specific receptors expressed by immune effector cells. ADO is produced from ATP through the enzymatic activities of CD39 and CD73. Alternatively, ADO can be generated starting from NAD+ , which is metabolized by the concerted action of CD38, CD203a/PC-1, and CD73. The role of ADO in immunity has been characterized in the last years in physiology and in pathological settings. This review examines a panel of reports focused on the functions of ADO in the context of human autoimmune/inflammatory diseases and the selected animal models...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29769005/adenosine-synthetic-methods-of-its-derivatives-and-antitumor-activity
#9
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/29768917/how-native-and-non-native-cations-bind-and-modulate-the-properties-of-gtp-atp
#10
Todor Dudev, Cedric Grauffel, Shang-Te Danny Hsu, Carmay Lim
Adenosine triphosphate (ATP) and guanosine triphosphate (GTP) exist in physiological solution mostly bound to cations. Interestingly, their cellular Mg2+ -bound forms have been shown to bind Li+ , a first-line drug for bipolar disorder. However, solution structures of NTP/NDP (N = A or G) bound to Li+ and/or Mg2+ have not been solved, thus precluding knowledge of how the native Mg2+ -bound cofactor conformation changes upon binding non-native Li+ and/or switching its environment from aqueous solution to proteins...
May 16, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29768061/structural-re-positioning-in-silico-molecular-modelling-oxidative-degradation-and-biological-screening-of-linagliptin-as-adenosine-3-receptor-adora3-modulators-targeting-hepatocellular-carcinoma
#11
Bassam M Ayoub, Yasmeen M Attia, Mahmoud S Ahmed
Chemical entities with structural diversity were introduced as candidates targeting adenosine receptor with different clinical activities, containing 3,7-dihydro-1H-purine-2,6-dione, especially adenosine 3 receptors (ADORA3). Our initial approach started with pharmacophore screening of ADORA3 modulators; to choose linagliptin (LIN), approved anti-diabetic drug as Dipeptidyl peptidase-4 inhibitors, to be studied for its modulating effect towards ADORA3. This was followed by generation, purification, analytical method development, and structural elucidation of oxidative degraded product (DEG)...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29767468/central-adenosine-a-1-receptors-inhibit-cough-via-suppression-of-excitatory-glutamatergic-and-tachykininergic-neurotransmission
#12
Ahmed Z El-Hashim, Seena Mathews, Fajer Al-Shamlan
BACKGROUND AND PURPOSE: The A1 adenosine receptor is reported to mediate several excitatory effects in the airways and has inhibitory effects in the central nervous system. In this study, we investigated the role of peripheral and central A1 adenosine receptors in regulating cough and airway obstruction. EXPERIMENTAL APPROACH: Drugs were administered to guinea pigs via the inhaled or intracerebroventricular (i.c.v.) routes. Cough was induced by exposing guinea pigs to aerosolised 0...
May 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29764507/aldolase-a-promotes-proliferation-and-g-1-s-transition-via-the-egfr-mapk-pathway-in-non-small-cell-lung-cancer
#13
Hailu Fu, Huijun Gao, Xiaoyu Qi, Lei Zhao, Donghua Wu, Yuxin Bai, Huimin Li, Xuan Liu, Jun Hu, Shujuan Shao
BACKGROUND: Our previous study demonstrated that aldolase A (ALDOA) is overexpressed in clinical human lung squamous cell carcinoma and that ALDOA promotes epithelial-mesenchymal transition and tumorigenesis. The present study aimed to explore the function of ALDOA in the modulation of non-small cell lung cancer (NSCLC) proliferation and cell cycle progression and the potential mechanism. METHODS: ALDOA was knocked down by short hairpin RNA in H520 and H1299 cells...
May 8, 2018: Cancer communications
https://www.readbyqxmd.com/read/29763615/anticancer-activity-study-of-a-3-adenosine-receptor-agonists
#14
Gabriella Marucci, Claudia Santinelli, Michela Buccioni, Aleix Martí Navia, Catia Lambertucci, Anastasia Zhurina, Olli Yli-Harja, Rosaria Volpini, Meenakshisundaram Kandhavelu
AIMS: A3 adenosine receptor (A3 AR) signalling activation seems to mediate anticancer effect, and it has been targeted for drug development. The identification of potent and selective A3 AR agonists could be crucial for cancer drug development. MATERIALS AND METHODS: In the present study was determined the in vitro activity of known 1-3 and newly 4-6 synthesized compounds with high A3 AR affinity and selectivity (Ki in the low nanomolar range) in binding studies...
May 13, 2018: Life Sciences
https://www.readbyqxmd.com/read/29761007/behavioral-changes-induced-through-adenosine-a2a-receptor-ligands-in-a-rat-depression-model-induced-by-olfactory-bulbectomy
#15
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/29758241/targeting-the-cd73-adenosine-axis-in-immuno-oncology
#16
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/29755479/lysophosphatidylcholine-promotes-phagosome-maturation-and-regulates-inflammatory-mediator-production-through-the-protein-kinase-a-phosphatidylinositol-3-kinase-p38-mitogen-activated-protein-kinase-signaling-pathway-during-mycobacterium-tuberculosis-infection
#17
Hyo-Ji Lee, Hyun-Jeong Ko, Dong-Kun Song, Yu-Jin Jung
Tuberculosis is caused by the infectious agent Mycobacterium tuberculosis (Mtb). Mtb has various survival strategies, including blockade of phagosome maturation and inhibition of antigen presentation. Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein and is involved in various cellular responses, such as activation of second messengers and bactericidal activity in neutrophils. In this study, macrophages were infected with a low infectious dose of Mtb and treated with LPC to investigate the bactericidal activity of LPC against Mtb...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755470/cd36-shunts-eicosanoid-metabolism-to-repress-cd14-licensed-interleukin-1%C3%AE-release-and-inflammation
#18
Karina F Zoccal, Luiz G Gardinassi, Carlos A Sorgi, Alyne F G Meirelles, Karla C F Bordon, Isaias Glezer, Palmira Cupo, Alessandra K Matsuno, Valdes R Bollela, Eliane C Arantes, Francisco S Guimarães, Lúcia Helena Faccioli
Interleukin (IL)-1β is a potential target for treatment of several inflammatory diseases, including envenomation by the scorpion Tityus serrulatus . In this context, bioactive lipids such as prostaglandin (PG)E2 and leukotriene (LT)B4 modulate the production of IL-1β by innate immune cells. Pattern recognition receptors (PRRs) that perceive T. serrulatus venom (TsV), and orchestrate LTB4 , PGE2 , and cyclic adenosine monophosphate (cAMP) production to regulate IL-1β release are unknown. Furthermore, molecular mechanisms driving human cell responses to TsV remain uncharacterized...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29753566/design-and-synthesis-of-2-6-disubstituted-8-amino-imidazo-1-2a-pyridines-a-promising-privileged-structure
#19
Rajaa Boulahjar, Angela Rincon Arias, Raphaël Bolteau, Nicolas Renault, Mathilde Coevoet, Amélie Barczyk, Romain Duroux, Saïd Yous, Patricia Melnyk, Laurence Agouridas
Imidazo[1,2a]pyridines have gained much interest in the field of medicinal chemistry research. In the aim of accessing new privileged structure, we decided to design and synthesize 8-aminated-imidazo[1,2a]pyridines substituted on positions 2 and 6. This scaffold, rarely found in the literature, was obtained via palladium-catalyzed coupling reactions (Suzuki reaction or N-hydroxysuccinimidyl activated ester method) and tested on adenosine receptor A2A . We demonstrated how incorporation of an exocyclic amine enhanced affinity towards this receptor while maintaining low cytotoxicity...
April 30, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29752618/tritium-labeled-agonists-as-tools-for-studying-adenosine-a-2b-receptors
#20
Sonja Hinz, Wessam M Alnouri, Ulrich Pleiss, Christa E Müller
A selective agonist radioligand for A2B adenosine receptors (A2B ARs) is currently not available. Such a tool would be useful for labeling the active conformation of the receptors. Therefore, we prepared BAY 60-6583, a potent and functionally selective A2B AR (partial) agonist, in a tritium-labeled form. Despite extensive efforts, however, we have not been able to establish a radioligand binding assay using [3 H]BAY 60-6583. This is probably due to its high non-specific binding and its moderate affinity, which had previously been overestimated based on functional data...
May 11, 2018: Purinergic Signalling
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