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Adenosine A2A receptor antagonists exert motor and neuroprotective effects by d...
Yu, Liqun; Shen, Hai-Ying; Coelho, Joana E.; Araújo, Inês M.; Huang, Qing-Yuan; Day, Yuan-Ji; Rebola, Nelson; Canas, Paula M.; Rapp, Erica KirstenTo investigate whether the motor and neuroprotective effects of adenosine A2A receptor (A2AR) antagonists are mediated by distinct cell types in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease.We used the forebrain A2AR knock-out mice coupled with flow cytometric analyses and intracerebroventricular injection to determine the contribution of A2ARs in forebrain neurons and gl...
Trkb receptors modulation of glutamate release is limited to a subset of nerve ...
Pereira, Daniela B.; Rebola, Nelson; Rodrigues, Ricardo J.; Cunha, Rodrigo A.; Carvalho, Arsélio P.; Duarte, Carlos B.Brain-derived neurotrophic factor (BDNF) modulates glutamatergic excitatory transmission in hippocampal primary cultures by acting at a presynaptic locus. Although it has been suggested that BDNF also modulates adult hippocampus glutamatergic transmission, this remains a matter of controversy. To clarify a putative role for this neurotrophin in the modulation of glutamate release we applied exogenous BDNF to is...
Long-term Effect of Convulsive Behavior on the Density of Adenosine A1 and A2A ...
Rebola, Nelson; Porciúncula, Lisiane O.; Lopes, Luísa V.; Oliveira, Catarina R.; Soares-da-Silva, Patrício; Cunha, Rodrigo A.Purpose: Adenosine is a neuromodulator that has been proposed to act as an anticonvulsant mainly via inhibitory A1 receptors, but recent data show that genetic deletion of facilitatory A2A receptors might also attenuate convulsions. Since both A1 and A2A receptors are prone to down- and upregulation in different stressful situations, we investigated if convulsive behavior leads to a long-term change in A1 and A...
Co-localization and functional interaction between adenosine A2A and metabotrop...
Rodrigues, Ricardo J.; Alfaro, Tiago M.; Rebola, Nelson; Oliveira, Catarina R.; Cunha, Rodrigo A.The anti-Parkinsonian effect of glutamate metabotropic group 5 (mGluR5) and adenosine A2A receptor antagonists is believed to result from their ability to postsynaptically control the responsiveness of the indirect pathway that is hyperfunctioning in Parkinson's disease. mGluR5 and A2A antagonists are also neuroprotective in brain injury models involving glutamate excitotoxicity. Thus, we hypothesized that the ...
Subcellular localization of adenosine A1 receptors in nerve terminals and synap...
Rebola, Nelson; Pinheiro, Paulo C.; Oliveira, Catarina R.; Malva, João O.; Cunha, Rodrigo A.Adenosine is a neuromodulator in the CNS that mainly acts through pre- and postsynaptic A1 receptors to inhibit the release of excitatory neurotransmitters and NMDA receptor function. This might result from a highly localized distribution of A1 receptors in the active zone and postsynaptic density of CNS synapses that we now investigated in the rat hippocampus. The binding density of the selective A1 receptor a...
Enhanced adenosine A2A receptor facilitation of synaptic transmission in the hi...
Rebola, Nelson; Sebastião, Ana M.; Mendonça, Alexandre de; Oliveira, Catarina R.; Ribeiro, J. A.; Cunha, Rodrigo A.Adenosine either inhibits or facilitates synaptic transmission through A1 or A2A receptors, respectively. Since A2A receptor density increases in the limbic cortex of aged (24 mo) compared with young adult rats (2 mo), we tested if A2A receptor modulation of synaptic transmission was also increased in aged rats. The A2A receptor agonist, CGS21680 (10 nM), caused a larger facilitation of the field excitatory pos...
Adenosine A3 receptors in the rat hippocampus: Lack of interaction with A1 rece...
Lopes, Luísa V.; Rebola, Nelson; Costenla, Ana Rita; Halldner, Linda; Jacobson, Marlene A.; Oliveira, Catarina R.; Richardson, Peter J.Adenosine acts as a neuromodulator in the hippocampus essentially through activation of inhibitory A1 receptors. Using single-cell PCR analysis, we found that CA1 pyramidal cells coexpress A1 receptor mRNA together with that of another adenosine receptor, the A3 receptor. As occurs for the A1 receptor, Western blot analysis indicated that the A3 receptor is also located in hippocampal nerve terminals. However, ...
Transducing system operated by adenosine A2A receptors to facilitate acetylchol...
Rebola, Nelson; Oliveira, Catarina R.; Cunha, Rodrigo A.Although molecular biology studies indicate the presence of adenosine A2A receptors in the rat hippocampus, the pharmacological characterization of adenosine A2A receptor binding and of its putative facilitatory effects has revealed features essentially different from these found for adenosine A2A receptors in most preparations. We now confirmed that activation of adenosine A2A receptors with 2-[4-(2-p-carboxye...
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