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Adenosine A2A and glutamate receptor

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https://www.readbyqxmd.com/read/29740323/the-selective-antagonism-of-adenosine-a-2b-receptors-reduces-the-synaptic-failure-and-neuronal-death-induced-by-oxygen-and-glucose-deprivation-in-rat-ca1-hippocampus-in-vitro
#1
Irene Fusco, Filippo Ugolini, Daniele Lana, Elisabetta Coppi, Ilaria Dettori, Lisa Gaviano, Daniele Nosi, Federica Cherchi, Felicita Pedata, Maria G Giovannini, Anna M Pugliese
Ischemia is a multifactorial pathology characterized by different events evolving in time. Immediately after the ischemic insult, primary brain damage is due to the massive increase of extracellular glutamate. Adenosine in the brain increases dramatically during ischemia in concentrations able to stimulate all its receptors, A1 , A2A , A2B , and A3 . Although adenosine exerts clear neuroprotective effects through A1 receptors during ischemia, the use of selective A1 receptor agonists is hampered by their undesirable peripheral side effects...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29740319/pharmacological-blockade-of-adenosine-a-2a-but-not-a-1-receptors-enhances-goal-directed-valuation-in-satiety-based-instrumental-behavior
#2
Yan Li, Xinran Pan, Yan He, Yang Ruan, Linshan Huang, Yuling Zhou, Zhidong Hou, Chaoxiang He, Zhe Wang, Xiong Zhang, Jiang-Fan Chen
The balance and smooth shift between flexible, goal-directed behaviors and repetitive, habitual actions are critical to optimal performance of behavioral tasks. The striatum plays an essential role in control of goal-directed versus habitual behaviors through a rich interplay of the numerous neurotransmitters and neuromodulators to modify the input, processing and output functions of the striatum. The adenosine receptors (namely A2A R and A1 R), with their high expression pattern in the striatum and abilities to interact and integrate dopamine, glutamate and cannabinoid signals in the striatum, may represent novel therapeutic targets for modulating instrumental behavior...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29688987/reduction-in-blood-glutamate-levels-combined-with-the-genetic-inactivation-of-a2ar-significantly-alleviate-traumatic-brain-injury-induced-acute-lung-injury
#3
Wei Bai, Ping Li, Ya-Lei Ning, Yu-Lin Jiang, Nan Yang, Xing Chen, Yuan-Guo Zhou
Traumatic brain injury-induced acute lung injury (TBI-ALI) is a serious complication of traumatic brain injury (TBI). Our previous clinical study found that high levels of blood glutamate after TBI were closely related to the occurrence and severity of TBI-ALI, while it remains unknown whether a high concentration of blood glutamate directly causes or aggravates TBI-ALI. We found that inhibition of the adenosine A2A receptor (A2AR) after brain injury alleviated the TBI-ALI; however, it is unknown whether lowering blood glutamate levels in combination with inhibiting the A2AR would lead to better effects...
April 23, 2018: Shock
https://www.readbyqxmd.com/read/29567422/neuroprotective-effect-of-idpu-1-7-imino-3-propyl-2-3-dihydrothiazolo-4-5-d-pyrimidin-6-7h-yl-urea-in-6-ohda-induced-rodent-model-of-hemiparkinson-s-disease
#4
Namrata Kumari, Saurabh Agrawal, Rita Kumari, Dimpy Sharma, Pratibha Mehta Luthra
Parkinson's disease (PD) is a progressive neurodegenerative motor disorder characterized by the degeneration of dopaminergic nigrostriatal neurons. Levodopa (L-DOPA) is the most effective therapy for PD, however, PD progression continues with significant side effects in long term, thus necessitating the search for effective therapy that impedes PD progression. PD therapy through non-dopaminergic pathways offers treatment without the risk of extrapyramidal effects. In this regard, earlier, we had reported, a novel compound IDPU with potential adenosine A2A receptor antagonist effect in haloperidol (chronic treatment) induced Parkinson model...
March 19, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29526759/adenosine-a-2a-receptor-inhibition-restores-the-normal-transport-of-endothelial-glutamate-transporters-in-the-brain
#5
Wei Bai, Ping Li, Ya-Lei Ning, Yan Peng, Ren-Ping Xiong, Nan Yang, Xing Chen, Yuan-Guo Zhou
Glutamate transporters (EAATs) on cerebral vascular endothelial cells play an important role in maintaining glutamate homeostasis in the brain. The dysfunction of endothelial EAATs is an important reason for the dramatically elevated brain glutamate levels after brain injury, such as traumatic brain injury (TBI). The adenosine A2A receptor (A2A R) plays an important role in regulating the brain glutamate level after brain injury; however, researchers have not clearly determined whether this role was related to its ability to regulate endothelial EAATs...
March 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29495349/neuroprotective-effects-and-mechanisms-of-tea-bioactive-components-in-neurodegenerative-diseases
#6
REVIEW
Shu-Qing Chen, Ze-Shi Wang, Yi-Xiao Ma, Wei Zhang, Jian-Liang Lu, Yue-Rong Liang, Xin-Qiang Zheng
As the population ages, neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) impose a heavy burden on society and families. The pathogeneses of PD and AD are complex. There are no radical cures for the diseases, and existing therapeutic agents for PD and AD have diverse side effects. Tea contains many bioactive components such as polyphenols, theanine, caffeine, and theaflavins. Some investigations of epidemiology have demonstrated that drinking tea can decrease the risk of PD and AD...
February 25, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29212737/astrocytic-lrp4-low-density-lipoprotein-receptor-related-protein-4-contributes-to-ischemia-induced-brain-injury-by-regulating-atp-release-and-adenosine-a-2a-r-adenosine-a2a-receptor-signaling
#7
Xin-Chun Ye, Jin-Xia Hu, Lei Li, Qiang Li, Fu-Lei Tang, Sen Lin, Dong Sun, Xiang-Dong Sun, Gui-Yun Cui, Lin Mei, Wen-Cheng Xiong
BACKGROUND AND PURPOSE: Lrp4 (low-density lipoprotein receptor-related protein 4) is predominantly expressed in astrocytes, where it regulates glutamatergic neurotransmission by suppressing ATP release. Here, we investigated Lrp4's function in ischemia/stroke-induced brain injury response, which includes glutamate-induced neuronal death and reactive astrogliosis. METHODS: The brain-specific Lrp4 conditional knockout mice (Lrp4GFAP-Cre ), astrocytic-specific Lrp4 conditional knockout mice (Lrp4GFAP-creER ), and their control mice (Lrp4f/f ) were subjected to photothrombotic ischemia and the transient middle cerebral artery occlusion...
January 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29205377/adenosine-a-2a-receptors-are-required-for-glutamate-mglur5-and-dopamine-d1-receptor-evoked-erk1-2-phosphorylation-in-rat-hippocampus-involvement-of-nmda-receptor
#8
Paraskevi Krania, Eleni Dimou, Maria Bantouna, Stylianos Kouvaros, Eirini Tsiamaki, Costas Papatheodoropoulos, Konstantinos Sarantis, Fevronia Angelatou
Interaction between mGluR5 and NMDA receptors (NMDAR) is vital for synaptic plasticity and cognition. We recently demonstrated that stimulation of mGluR5 enhances NMDAR responses in hippocampus by phosphorylating NR2B(Tyr1472) subunit, and this reaction was enabled by adenosine A2A receptors (A2A R) (J Neurochem, 135, 2015, 714). In this study, by using in vitro phosphorylation and western blot analysis in hippocampal slices of male Wistar rats, we show that mGluR5 stimulation or mGluR5/NMDARs co-stimulation synergistically activate ERK1/2 signaling leading to c-Fos expression...
December 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28844595/cognitive-impairments-associated-with-alterations-in-synaptic-proteins-induced-by-the-genetic-loss-of-adenosine-a2a-receptors-in-mice
#9
Maria Moscoso-Castro, Marc López-Cano, Irene Gracia-Rubio, Francisco Ciruela, Olga Valverde
The study of psychiatric disorders usually focuses on emotional symptoms assessment. However, cognitive deficiencies frequently constitute the core symptoms, are often poorly controlled and handicap individual's quality of life. Adenosine receptors, through the control of both dopamine and glutamate systems, have been implicated in the pathophysiology of several psychiatric disorders such as schizophrenia and attention deficit/hyperactivity disorder. Indeed, clinical data indicate that poorly responsive schizophrenia patients treated with adenosine adjuvants show improved treatment outcomes...
August 26, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28725181/impact-of-proestrus-on-gene-expression-in-the-medial-preoptic-area-of-mice
#10
Csaba Vastagh, Zsolt Liposits
The antero-ventral periventricular zone (AVPV) and medial preoptic area (MPOA) have been recognized as gonadal hormone receptive regions of the rodent brain that-via wiring to gonadotropin-releasing hormone (GnRH) neurons-contribute to orchestration of the preovulatory GnRH surge. We hypothesized that neural genes regulating the induction of GnRH surge show altered expression in proestrus. Therefore, we compared the expression of 48 genes obtained from intact proestrous and metestrous mice, respectively, by quantitative real-time PCR (qPCR) method...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28377741/adenosine-a2a-receptor-gene-knockout-prevents-l-3-4-dihydroxyphenylalanine-induced-dyskinesia-by-downregulation-of-striatal-gad67-in-6-ohda-lesioned-parkinson-s-mice
#11
Su-Bing Yin, Xiao-Guang Zhang, Shuang Chen, Wen-Ting Yang, Xia-Wei Zheng, Guo-Qing Zheng
l-3,4-Dihydroxyphenylalanine (l-DOPA) remains the primary pharmacological agent for the symptomatic treatment of Parkinson's disease (PD). However, the development of l-DOPA-induced dyskinesia (LID) limits the long-term use of l-DOPA for PD patients. Some data have reported that adenosine A2A receptor (A2AR) antagonists prevented LID in animal model of PD. However, the mechanism in which adenosine A2AR blockade alleviates the symptoms of LID has not been fully clarified. Here, we determined to knock out (KO) the gene of A2AR and explored the possible underlying mechanisms implicated in development of LID in a mouse model of PD...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28120151/the-ying-and-yang-of-adenosine-a-1-and-a-2a-receptors-on-erk1-2-activation-in-a-rat-model-of-global-cerebral-ischemia-reperfusion-injury
#12
Reham M Atef, Azza M Agha, Abdel-Rahman A Abdel-Rhaman, Noha N Nassar
Adenosine impacts cerebral ischemia reperfusion (IR) through the inhibitory A1 and the excitatory A2 receptors. The present study aimed at investigating the contrasting role of pERK1/2 in mediating adenosine A1 R (protective) versus A2A R (deleterious) effects in IR. Male Wistar rats subjected to bilateral carotid occlusion (45 min) followed by reperfusion (24 h) exhibited increased pERK1/2 activity, downstream from DAG pathway, along with increases in hippocampal glutamate, c-Fos, NF-κB, TNF-α, iNOS, TBARS, cytochrome c, caspase-3, BDNF, Nrf2, and IL-10 contents...
February 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/28071892/transient-adenosine-release-is-modulated-by-nmda-and-gaba-b-receptors
#13
Michael D Nguyen, Ying Wang, Mallikarjunarao Ganesana, B Jill Venton
Adenosine is a neuroprotective agent that modulates neurotransmission and is modulated by other neurotransmitters. Spontaneous, transient adenosine is a recently discovered mode of signaling where adenosine is released and cleared from the extracellular space quickly, in less than three seconds. Spontaneous adenosine release is regulated by adenosine A1 and A2a receptors, but regulation by other neurotransmitter receptors has not been studied. Here, we examined the effect of glutamate and GABA receptors on the concentration and frequency of spontaneous, transient adenosine release by measuring adenosine with fast-scan cyclic voltammetry in the rat caudate-putamen...
February 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28012867/chronic-oral-administration-of-mpep-an-antagonist-of-mglu5-receptor-during-gestation-and-lactation-alters-mglu5-and-a2a-receptors-in-maternal-and-neonatal-brain
#14
Antonio López-Zapata, David Agustín León-Navarro, María Crespo, José Luis Albasanz, Mairena Martín
Antidepressant and anxiolytic drugs are widely consumed even by pregnant and lactating women. The metabotropic glutamate receptor 5 (mGlu5) antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) exerts antidepressant- and anxiolytic-like actions. Given that treatment for anxiety and depression use to be prolonged in time, it is conceivable a possible modulation of metabotropic glutamate receptors (mGlu receptors) after prolonged MPEP exposure, which could also modify adenosine A2A receptors (A2AR) since functional cross-talk between them has been reported...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27663541/caffeine-alters-glutamate-aspartate-transporter-function-and-expression-in-rat-retina
#15
Adriana Pinto de Freitas, Danielle Dias Pinto Ferreira, Arlete Fernandes, Robertta Silva Martins, Vladimir Pedro Peralva Borges-Martins, Matheus Figueiredo Sathler, Maurício Dos-Santos-Pereira, Roberto Paes-de-Carvalho, Elizabeth Giestal-de-Araujo, Ricardo Augusto de Melo Reis, Regina Celia Cussa Kubrusly
l-Glutamate and l-aspartate are the main excitatory amino acids (EAAs) in the Central Nervous System (CNS) and their uptake regulation is critical for the maintenance of the excitatory balance. Excitatory amino acid transporters (EAATs) are widely distributed among central neurons and glial cells. GLAST and GLT1 are expressed in glial cells, whereas excitatory amino acid transporter 3/excitatory amino acid carrier 1 (EAAT3/EAAC1) is neuronal. Different signaling pathways regulate glutamate uptake by modifying the activity and expression of EAATs...
November 19, 2016: Neuroscience
https://www.readbyqxmd.com/read/27577098/current-and-experimental-treatments-of-parkinson-disease-a-guide-for-neuroscientists
#16
REVIEW
Wolfgang Oertel, Jörg B Schulz
Over a period of more than 50 years, the symptomatic treatment of the motor symptoms of Parkinson disease (PD) has been optimized using pharmacotherapy, deep brain stimulation, and physiotherapy. The arsenal of pharmacotherapies includes L-Dopa, several dopamine agonists, inhibitors of monoamine oxidase (MAO)-B and catechol-o-methyltransferase (COMT), and amantadine. In the later course of the disease, motor complications occur, at which stage different oral formulations of L-Dopa or dopamine agonists with long half-life, a transdermal application or parenteral pumps for continuous drug supply can be subscribed...
October 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27365148/how-does-adenosine-control-neuronal-dysfunction-and-neurodegeneration
#17
REVIEW
Rodrigo A Cunha
The adenosine modulation system mostly operates through inhibitory A1 (A1 R) and facilitatory A2A receptors (A2A R) in the brain. The activity-dependent release of adenosine acts as a brake of excitatory transmission through A1 R, which are enriched in glutamatergic terminals. Adenosine sharpens salience of information encoding in neuronal circuits: high-frequency stimulation triggers ATP release in the 'activated' synapse, which is locally converted by ecto-nucleotidases into adenosine to selectively activate A2A R; A2A R switch off A1 R and CB1 receptors, bolster glutamate release and NMDA receptors to assist increasing synaptic plasticity in the 'activated' synapse; the parallel engagement of the astrocytic syncytium releases adenosine further inhibiting neighboring synapses, thus sharpening the encoded plastic change...
December 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27230697/nondopaminergic-treatments-for-parkinson-s-disease-current-and-future-prospects
#18
REVIEW
Maria Eliza Freitas, Susan H Fox
Parkinson's disease is primarily caused by dysfunction of dopaminergic neurons, however, nondopaminergic (ND) systems are also involved. ND targets are potentially useful to reduce doses of levodopa or to treat nonlevodopa-responsive symptoms. Recent studies have investigated the role of ND drugs for motor and nonmotor symptoms. Adenosine A2A receptor antagonists, mixed inhibitors of sodium/calcium channels and monoamine oxidase-B have recently been found to improve motor fluctuations. N-methyl-d-aspartate receptor antagonists and serotonin 5HT1B receptor agonists demonstrated benefit in levodopa-induced dyskinesia...
June 2016: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/27127992/functional-role-of-striatal-a2a-d2-and-mglu5-receptor-interactions-in-regulating-striatopallidal-gaba-neuronal-transmission
#19
Sarah Beggiato, Maria Cristina Tomasini, Andrea Celeste Borelli, Dasiel Oscar Borroto-Escuela, Kjell Fuxe, Tiziana Antonelli, Sergio Tanganelli, Luca Ferraro
In this study, the functional role of individual striatal receptors for adenosine (A2AR), dopamine (D2R), and the metabotropic glutamate receptor mGlu5R in regulating rat basal ganglia activity was characterized in vivo using dual-probe microdialysis in freely moving rats. In particular, intrastriatal perfusion with the D2R agonist quinpirole (10 μM, 60 min) decreased ipsilateral pallidal GABA and glutamate levels, whereas intrastriatal CGS21680 (A2AR agonist; 1 μM, 60 min) was ineffective on either pallidal GABA and glutamate levels or the quinpirole-induced effects...
July 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27068462/differential-dopamine-regulation-of-ca-2-signaling-and-its-timing-dependence-in-the-nucleus-accumbens
#20
Immani Swapna, Brian Bondy, Hitoshi Morikawa
Dopamine action in the nucleus accumbens (NAc) is thought to drive appetitive behavior and Pavlovian reward learning. However, it remains controversial how dopamine achieves these behavioral effects by regulating medium spiny projection neurons (MSNs) of the NAc, especially on a behaviorally relevant timescale. Metabotropic glutamate receptor (mGluR)-induced Ca(2+) signaling dependent on the Ca(2+)- releasing messenger inositol 1,4,5-triphosphate (IP3) plays a critical role in controlling neuronal excitability and synaptic plasticity...
April 19, 2016: Cell Reports
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