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Adenosine A2A receptors control the extracellular levels of adenosine through modulation of nucleoside transporters activity in the rat hippocampus

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Resumo:Adenosine, a neuromodulator of the CNS, activates inhibitory- A1 receptors and facilitatory-A2A receptors; its synaptic levels are controlled by the activity of bi-directional equilibrative nucleoside transporters. To study the relationship between the extracellular formation/inactivation of adenosine and the activation of adenosine receptors, we investigated how A1 and A2A receptor activation modifies adenosine transport in hippocampal synaptosomes. The A2A receptor agonist, CGS 21680 (30 nM), facilitated adenosine uptake through a PKCdependent mechanism, but A1 receptor activation had no effect. CGS 21680 (30 nM) also increased depolarization-induced release of adenosine. Both effects were prevented by A2A receptor blockade. A2A receptor-mediated enhancement of adenosine transport system is important for formatting adenosine neuromodulation according to the stimulation frequency, as: (1) A1 receptor antagonist, DPCPX (250 nM), facilitated the evoked release of [3H]acetylcholine under lowfrequency stimulation (2 Hz) from CA3 hippocampal slices, but had no effect under high-frequency stimulation (50 Hz); (2)either nucleoside transporter or A2A receptor blockade revealed the facilitatory effect of DPCPX (250 nM) on [3H]acetylcholine evoked-release triggered by high-frequency stimulation. These results indicate that A2A receptor activation facilitates the activity of nucleoside transporters, which have a preponderant role in modulating the extracellular adenosine levels available to activate A1 receptors.
Autores principais:Duarte, António Pinto
Outros Autores:Coelho, Joana E.; Cunha, Rodrigo A.; Ribeiro, Joaquim Alexandre; Sebastião, Ana M
Assunto:A2A receptors Acetylcholine Adenosine Hippocampus Nucleoside transporters Stimulation frequency
Ano:2005
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa

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