Navegando por Assunto "Receptor A2A de adenosina"

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Acesso aberto (Open Access)
Investigação dos efeitos da cafeína e SCH58261 sobre as alterações comportamentais e no estresse oxidativo, e papel dos receptores A2A na potenciação de longo prazo após intoxicação por etanol em padrão binge em ratos fêmeas da adolescência a fase adulta
(Universidade Federal do Pará, 2022-11) PINHEIRO, Bruno Gonçalves; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
Introduction: Binge consumption of ethanol is an intermittent and episodic pattern of ingestion involved in several brain disorders that affect adolescents, considered more susceptible to damage that persists into adulthood. In the deleterious effects of ethanol, an important intoxication mechanism is the overproduction of adenosine, which causes hyperexcitability in its receptors, generating behavioral changes and oxidative stress. These receptors are antagonized by caffeine, a bioactive compound that can modulate the deleterious overactivation of ethanol. Objective: The aim of this study was to investigate the effects of caffeine administration on behavioral changes related to locomotion, anxiety, cognition and oxidative balance induced by ethanol in the binge drinking pattern during adolescence. In addition, it aims to assess the contribution of A2A receptors in the observed changes, including long-term potentiation (LTP). Material and Methods: Female Wistar rats (35 days old; n = 102) were allocated into six groups: control (distilled water, v.o), ethanol (3 g/kg/day; 3 days on-4 days off, v.o) , caffeine (10 mg/kg/day, v.o), caffeine + ethanol, A2A antagonist SCH58261 (0.1 mg/kg/day, intraperitoneal - i,p) and ethanol + SCH58261. The animals were submitted to open field behavioral tests, object recognition and elevated plus maze. The oxidative biochemistry parameters of trolox equivalent antioxidant capacity (TEAC), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) in the pre- frontal and hippocampus. LTP recordings in the medial prefrontal cortex (mPFC), ventral (vHip) and dorsal (dHIP) portions of the hippocampus of the control, ethanol, ethanol + SCH58261 and SCH58261 groups were evaluated through electrophysiology. Results: Caffeine prevented ethanol-induced behavioral impairments, including by blocking A2A receptors. In addition, it attenuated the oxidative stress induced by binge drinking by alternative A2A receptor pathways. Blockade of A2A receptors increased LTP levels in mPFC and vHIP, however decreased in dHIP. Conclusion: Caffeine showed neuroprotection in behavioral changes and oxidative stress induced by the binge drinking model in adolescent rats. In addition, blockade of A2A receptors mitigated the observed behavioral changes, with improvement of LTP levels in the prefrontal cortex and hippocampus, which suggests the contribution of this pathway to neuroprotection in deficits induced by ethanol exposure during adolescence.
Acesso aberto (Open Access)
Receptor A2A de adenosina modula o transporte de glutamato independente de sodio em cultura primaria de celulas da retina
(Universidade Federal do Pará, 2024-11) LIMA, Caroline Araujo Costa de; OLIVEIRA, Karen Renata Herculano Matos; http://lattes.cnpq.br/3032008039259369
Dysregulation of extracellular glutamate levels is directly associated with several CNS pathologies, highlighting the importance of glutamate transporters in maintaining tissue homeostasis and developing new therapeutic approaches. The retina is particularly vulnerable toexcitotoxic events due to its high levels of glutamate extracelular and the frequente exposure to oxidative stimuli, reinforcing the need for regulatory mecanisms to preserve retinal physiology. In this context, adenosine emerges as an essential neuromodulator, exhibiting regulatory effects that are concentration- and receptor-dependent. Therefore, the objetive of this study was to characterize the effect of adenosine on sodium-independent glutamate transport in retinal cell culture. As such, mixed primary cell cultures from White leghorn chick embryos (E7-E8) were maintained for 7 days in DMEM+10% FBS at 37°C and 5% CO₂. The cells were submitted to apre-incubation with an A2A receptor blocker and incubated with different adenosine concentrations for glutamate release and uptake assays. Glutamate levels were quantified by HPLC, and protein levels were measured by the Bradford method, with equimolar substitution of NaCl by LiCl. Furthermore, immunofluorescence with an anti-xCT antibody and the nuclear marker DAPI was used to identify the sodium-independent glutamate transporter, with image analysis performed using ImageJ e Photoshop CS6. Statistical analysis was conducted using Student’s test T and ANOVA one-way with Tukey post-hoc test via GraphPad 9.0, with data expressed as percentage of control±S.D. with p<0,05. The results confirmed the expression of the xCT subunit, indicating that the system xCG-is the sodium-independent glutamate transporter in retinal cells. Additionally, adenosine at a concentration of 50μM increased glutamate release by approximately 800%, while glutamate sodium-independent uptake was completely inhibited.These effects were fully by A2A receptor blockade. Therefore, we demonstrated that activation of the A2A receptor modulates glutamate sodium independent transport, whose