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Adenosine A2A and glutamate receptor

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https://www.readbyqxmd.com/read/27663541/caffeine-alters-glutamate-aspartate-transporter-function-and-expression-in-rat-retina
#1
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...
September 20, 2016: Neuroscience
https://www.readbyqxmd.com/read/27577098/current-and-experimental-treatments-of-parkinson-disease-a-guide-for-neuroscientists
#2
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
#3
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...
July 1, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27230697/nondopaminergic-treatments-for-parkinson-s-disease-current-and-future-prospects
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/27012890/glun1-deletions-in-d1-and-a2a-expressing-cell-types-reveal-distinct-modes-of-behavioral-regulation
#7
Max E Joffe, Sophie R Vitter, Brad A Grueter
N-methyl-d-aspartate receptors (NMDARs) are profound regulators of glutamate neurotransmission and behavior. To coordinate components of the limbic system, the dorsal and ventral striatum integrate cognitive and emotional information towards the execution of complex behaviors. Striatal outflow is conveyed by medium spiny neurons (MSNs), which can be dichotomized by expression of dopamine receptor subtype 1 (D1) or adenosine receptor subtype 2A (A2A). To examine how striatal NMDAR function modulates reward-related behaviors, we generated D1- and A2A-specific genetic deletions of the obligatory GluN1 subunit...
January 2017: Neuropharmacology
https://www.readbyqxmd.com/read/26860412/caffeine-reverts-memory-but-not-mood-impairment-in-a-depression-prone-mouse-strain-with-up-regulated-adenosine-a2a-receptor-in-hippocampal-glutamate-synapses
#8
Nuno J Machado, Ana Patrícia Simões, Henrique B Silva, Ana Paula Ardais, Manuella P Kaster, Pedro Garção, Diana I Rodrigues, Daniela Pochmann, Ana Isabel Santos, Inês M Araújo, Lisiane O Porciúncula, Ângelo R Tomé, Attila Köfalvi, Jean-Marie Vaugeois, Paula Agostinho, Malika El Yacoubi, Rodrigo A Cunha, Catarina A Gomes
Caffeine prophylactically prevents mood and memory impairments through adenosine A2A receptor (A2AR) antagonism. A2AR antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression...
February 9, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/26858178/combined-effects-of-simultaneous-exposure-to-caffeine-and-cocaine-in-the-mouse-striatum
#9
Javier A Muñiz, Gimena Gomez, Betina González, María Celeste Rivero-Echeto, Jean Lud Cadet, Edgar García-Rill, Francisco J Urbano, Veronica Bisagno
Caffeine is the world's most popular psychoactive drug and is also an active adulterant found in many drugs of abuse, including seized cocaine samples. Despite several studies which examine the effects of caffeine or cocaine administered as single agents, little data are available for these agents when given in combination. The purpose of the present study was to determine if combined intake of both psychostimulants can lead to maladaptive changes in striatal function. Mice were injected with a binge regimen (intermittent treatment for 13 days) of caffeine (3 × 5 mg/kg), cocaine (3 × 10 mg/kg), or combined administration...
May 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/26791215/local-control-of-extracellular-dopamine-levels-in-the-medial-nucleus-accumbens-by-a-glutamatergic-projection-from-the-infralimbic-cortex
#10
César Quiroz, Marco Orrú, William Rea, Andrés Ciudad-Roberts, Gabriel Yepes, Jonathan P Britt, Sergi Ferré
It is generally assumed that infralimbic cortex (ILC) and prelimbic cortex, two adjacent areas of the medial prefrontal cortex (mPFC) in rodents, provide selective excitatory glutamatergic inputs to the nucleus accumbens (NAc) shell and core, respectively. It is also generally believed that mPFC influences the extracellular levels of dopamine in the NAc primarily by an excitatory collateral to the ventral tegmental area (VTA). In the present study, we first established the existence of a selective functional connection between ILC and the posteromedial portions of the VTA (pmVTA) and the mNAc shell (pmNAc shell), by measuring striatal neuronal activation (immunohistochemical analysis of ERK1/2 phosphorylation) and glutamate release (in vivo microdialysis) upon ILC electrical stimulation...
January 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26762803/major-dorsoventral-differences-in-the-modulation-of-the-local-ca1-hippocampal-network-by-nmda-mglu5-adenosine-a2a-and-cannabinoid-cb1-receptors
#11
S Kouvaros, C Papatheodoropoulos
Recent research points to diversification in the local neuronal circuitry between dorsal (DH) and ventral (VH) hippocampus that may be involved in the large-scale functional segregation along the long axis of the hippocampus. Here, using CA1 field recordings from rat hippocampal slices, we show that activation of N-methyl-d-aspartate receptors (NMDARs) reduced excitatory transmission more in VH than in DH, with an adenosine A1 receptor-independent mechanism, and reduced inhibition and enhanced postsynaptic excitability only in DH...
March 11, 2016: Neuroscience
https://www.readbyqxmd.com/read/26742520/guanosine-anxiolytic-like-effect-involves-adenosinergic-and-glutamatergic-neurotransmitter-systems
#12
Roberto Farina Almeida, Daniel Diniz Comasseto, Denise Barbosa Ramos, Gisele Hansel, Eduardo R Zimmer, Samanta Oliveira Loureiro, Marcelo Ganzella, Diogo Onofre Souza
Accumulating evidences indicate that endogenous modulators of excitatory synapses in the mammalian brain are potential targets for treating neuropsychiatric disorders. Indeed, glutamatergic and adenosinergic neurotransmissions were recently highlighted as potential targets for developing innovative anxiolytic drugs. Accordingly, it has been shown that guanine-based purines are able to modulate both adenosinergic and glutamatergic systems in mammalian central nervous system. Here, we aimed to investigate the potential anxiolytic-like effects of guanosine and its effects on the adenosinergic and glutamatergic systems...
January 7, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/26642806/role-of-adenosine-a2a-receptor-in-cerebral-ischemia-reperfusion-injury-signaling-to-phosphorylated-extracellular-signal-regulated-protein-kinase-perk1-2
#13
R A Mohamed, A M Agha, A A Abdel-Rahman, N N Nassar
Following brain ischemia reperfusion (IR), the dramatic increase in adenosine activates A2AR to induce further neuronal damage. Noteworthy, A2A antagonists have proven efficacious in halting IR injury, however, the detailed downstream signaling remains elusive. To this end, the present study aimed to investigate the possible involvement of phospho-extracellular signal-regulated kinase (pERK1/2) pathway in mediating protection afforded by the central A2A blockade. Male Wistar rats (250-270 g) subjected to bilateral carotid occlusion for 45 min followed by a 24-h reperfusion period showed increased infarct size corroborating histopathological damage, memory impairment and motor incoordination as well as increased locomotor activity...
February 9, 2016: Neuroscience
https://www.readbyqxmd.com/read/26639458/mglu5-dopamine-d2-and-adenosine-a2a-receptors-in-l-dopa-induced-dyskinesias
#14
REVIEW
Nicolas Morin, Marc Morissette, Laurent Grégoire, Thérèse Di Paolo
Patients with Parkinson's disease (PD) receiving L-3,4-dihydroxyphenylalanine (L-DOPA, the gold-standard treatment for this disease) frequently develop abnormal involuntary movements, termed L-DOPA-induced dyskinesias (LID). Glutamate overactivity is well documented in PD and LID. An approach to manage LID is to add to L-DOPA specific agents to reduce dyskinesias such as metabotropic glutamate receptor (mGlu receptor) drugs. This article reviews the contribution of mGlu type 5 (mGlu5) receptors in animal models of PD...
2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/26622427/effect-of-adenosine-on-glast-expression-in-the-retina-of-a-chronic-ocular-hypertension-rat-model
#15
Zi-Jian Yang, Yi-Sheng Zhong
This study was performed to evaluate the effect of adenosine and an adenosine receptor antagonist on the expression of the L-glutamate/L-aspartate transporter (GLAST) in the retina of a chronic ocular hypertension (COH) rat model. COH models were established via the cauterization of three episcleral veins. Measurements of the intraocular pressure of the right eye (COH eye) were taken weekly by a handheld digital tonometer. A total of 10 µM adenosine or 10 µM adenosine + 100 nM SCH442416 solution (2 µl) was injected into the rat vitreous space...
September 2015: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/26581499/purinergic-signalling-in-brain-ischemia
#16
REVIEW
Felicita Pedata, Ilaria Dettori, Elisabetta Coppi, Alessia Melani, Irene Fusco, Renato Corradetti, Anna Maria Pugliese
Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia a primary damage due to the early massive increase of extracellular glutamate is followed by activation of resident immune cells, i.e microglia, and production or activation of inflammation mediators. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. Extracellular concentrations of ATP and adenosine in the brain increase dramatically during ischemia in concentrations able to stimulate their respective specific P2 and P1 receptors...
May 2016: Neuropharmacology
https://www.readbyqxmd.com/read/26526685/striatal-adenosine-cannabinoid-receptor-interactions-in-rats-over-expressing-adenosine-a2a-receptors
#17
Valentina Chiodi, Antonella Ferrante, Luca Ferraro, Rosa Luisa Potenza, Monica Armida, Sarah Beggiato, Antonella Pèzzola, Michael Bader, Kjell Fuxe, Patrizia Popoli, Maria Rosaria Domenici
Adenosine A2A receptors (A2 A Rs) and cannabinoid CB1 receptors (CB1 Rs) are highly expressed in the striatum, where they functionally interact and form A2A /CB1 heteroreceptor complexes. We investigated the effects of CB1 R stimulation in a transgenic rat strain over-expressing A2 A Rs under the control of the neural-specific enolase promoter (NSEA2A rats) and in age-matched wild-type (WT) animals. The effects of the CB1 R agonist WIN 55,212-2 (WIN) were significantly lower in NSEA2A rats than in WT animals, as demonstrated by i) electrophysiological recordings of synaptic transmission in corticostriatal slices; ii) the measurement of glutamate outflow from striatal synaptosomes and iii) in vivo experiments on locomotor activity...
March 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/26522273/helix-3-acts-as-a-conformational-hinge-in-class-a-gpcr-activation-an-analysis-of-interhelical-interaction-energies-in-crystal-structures
#18
Isaias Lans, James A R Dalton, Jesús Giraldo
A collection of crystal structures of rhodopsin, β2-adrenergic and adenosine A2A receptors in active, intermediate and inactive states were selected for structural and energetic analyses to identify the changes involved in the activation/deactivation of Class A GPCRs. A set of helix interactions exclusive to either inactive or active/intermediate states were identified. The analysis of these interactions distinguished some local conformational changes involved in receptor activation, in particular, a packing between the intracellular domains of transmembrane helices H3 and H7 and a separation between those of H2 and H6...
December 2015: Journal of Structural Biology
https://www.readbyqxmd.com/read/26452489/adenosine-a2a-receptor-activation-is-determinant-for-bdnf-actions-upon-gaba-and-glutamate-release-from-rat-hippocampal-synaptosomes
#19
Sandra Henriques Vaz, Sofia Rapaz Lérias, Sara Parreira, Maria José Diógenes, Ana Maria Sebastião
Adenosine, through A(2A) receptor (A(2A)R) activation, can act as a metamodulator, controlling the actions of other modulators, as brain-derived neurotrophic factor (BDNF). Most of the metamodulatory actions of adenosine in the hippocampus have been evaluated in excitatory synapses. However, adenosine and BDNF can also influence GABAergic transmission. We thus evaluated the role of A(2A)R on the modulatory effect of BDNF upon glutamate and GABA release from isolated hippocampal nerve terminals (synaptosomes)...
December 2015: Purinergic Signalling
https://www.readbyqxmd.com/read/26303340/adenosine-a%C3%A2-a-receptors-permit-mglur5-evoked-tyrosine-phosphorylation-of-nr2b-tyr1472-in-rat-hippocampus-a-possible-key-mechanism-in-nmda-receptor-modulation
#20
Konstantinos Sarantis, Eirini Tsiamaki, Stylianos Kouvaros, Costas Papatheodoropoulos, Fevronia Angelatou
A great body of evidence points toward a functional interaction between metabotropic glutamate 5 receptors (mGluR5) and NMDA receptors (NMDAR) that enhances synaptic plasticity and cognition. However, the molecular mechanism underlying this interaction remains unclear. Here, we show that co-activation of mGluR5 and NMDAR in hippocampal slices synergistically leads to a robust phosphorylation of NR2B (Tyr1472), which is Src kinase dependent and is enabled by endogenous adenosine acting on A2A receptors. As it is well known, NR2B (Tyr1472) phosphorylation anchors NR2B-containing NMDARs to the surface of post-synaptic membranes, preventing their internalization...
November 2015: Journal of Neurochemistry
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