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Adenosine A2A receptor activation is determinant for BDNF actions upon GABA and glutamate release from rat hippocampal synaptosomes

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Abstract

Adenosine, through A2A receptor (A2AR) 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 A2AR on the modulatory effect of BDNF upon glutamate and GABA release from isolated hippocampal nerve terminals (synaptosomes). BDNF (30 ng/ml) enhanced K+-evoked [3H]glutamate release and inhibited the K+-evoked [3H]GABA release from synaptosomes. The effect of BDNF on both glutamate and GABA release requires tonic activation of adenosine A2AR since for both neurotransmitters, the BDNF action was blocked by the A2AR antagonist SCH 58261 (50 nM). In the presence of the A2AR agonist, CGS21680 (30 nM), the effect of BDNF on either glutamate or GABA release was, however, not potentiated. It is concluded that both the inhibitory actions of BDNF on GABA release as well as the facilitatory action of the neurotrophin on glutamate release are dependent on the activation of adenosine A2AR by endogenous adenosine. However, these actions could not be further enhanced by exogenous activation of A2AR.

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Acknowledgements

We thank Regeneron Pharmaceuticals for the gift of brain-derived neurotrophic factor and the Institute of Physiology of the Faculty of Medicine of Lisbon for the animal housing facility. This work was supported by “Fundação para a Ciência e a Tecnologia” Grant SFRH/BPD/81627/2011 (to S. H. V.) and by “Educação pela Ciência” program, GAPIC/Faculty of Medicine of the University of Lisbon (to S.R.L. and S.P.).

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    Authors and Affiliations

    1. Instituto de Medicina Molecular, Faculty of Medicine and Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Av. Prof. Egas Moniz, Ed. Egas Moniz, Piso 1B, Lisbon, 1649-028, Portugal

      Sandra Henriques Vaz, Sofia Rapaz Lérias, Sara Parreira, Maria José Diógenes & Ana Maria Sebastião

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    1. Sandra Henriques Vaz
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    2. Sofia Rapaz Lérias
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    3. Sara Parreira
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    4. Maria José Diógenes
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    5. Ana Maria Sebastião
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    Correspondence to Sandra Henriques Vaz.

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    Sandra Henriques Vaz, Sofia Rapaz Lérias and Sara Parreira contributed equally to this work.

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    Vaz, S., Lérias, S.R., Parreira, S. et al. Adenosine A2A receptor activation is determinant for BDNF actions upon GABA and glutamate release from rat hippocampal synaptosomes. Purinergic Signalling 11, 607–612 (2015). https://doi.org/10.1007/s11302-015-9476-1

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