title: Adenosine A2A receptor activation is determinant for BDNF actions upon GABA and glutamate release from rat hippocampal synaptosomes.
abstract: 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). BDNF (30 ng/ml) enhanced K(+)-evoked [(3)H]glutamate release and inhibited the K(+)-evoked [(3)H]GABA release from synaptosomes. The effect of BDNF on both glutamate and GABA release requires tonic activation of adenosine A(2A)R since for both neurotransmitters, the BDNF action was blocked by the A(2A)R antagonist SCH 58261 (50 nM). In the presence of the A(2A)R 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 A(2A)R by endogenous adenosine. However, these actions could not be further enhanced by exogenous activation of A(2A)R.
authors.affiliation: 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. svaz@medicina.ulisboa.pt.
authors.forename: Sandra Henriques
authors.initials: SH
authors.lastname: Vaz
authors.affiliation: 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.
authors.forename: Sofia Rapaz
authors.initials: SR
authors.lastname: Lérias
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: Parreira
authors.affiliation: 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.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Diógenes
authors.affiliation: 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.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Sebastião
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D010627:Phenethylamines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D019208:Brain-Derived Neurotrophic Factor; D010627:Phenethylamines; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D011188:Potassium
keywords: Adenosine A2A receptors; Brain-derived neurotrophic factor; GABA release; Glutamate release; Hippocampus; Synaptosomes