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Brain-derived neurotrophic factor facilitates glutamate and inhibits GABA release from hippocampal synaptosomes through different mechanisms

2004; Elsevier BV; Volume: 1016; Issue: 1 Linguagem: Inglês

10.1016/j.brainres.2004.04.070

1872-6240

Nuno Canas, Inês Tomás Pereira, Joaquim A. Ribeiro, Ana M. Sebastião,

Neuroscience and Neuropharmacology Research

Brain-derived neurotrophic factor (BDNF) has an acute excitatory effect on rat hippocampal synaptic transmission. To compare the action of BDNF upon the release of excitatory and inhibitory neurotransmitters in the hippocampus, we studied the effect of acutely applied BDNF on the K+-evoked glutamate and on the K+-evoked γ-aminobutyric acid (GABA) release from rat hippocampal nerve terminals (synaptosomes). The acute application of BDNF (30–100 ng/ml) enhanced the K+-evoked [3H]glutamate release. This effect involved tyrosine-kinase B (TrkB) receptor phosphorylation and Ca2+ entry into synaptosomes through voltage-sensitive calcium channels, since it was abolished by K252a (200 nM), which prevents TrkB-mediated phosphorylation, and by CdCl2 (0.2 mM), a blocker of voltage-sensitive calcium channels. In contrast, BDNF (3–100 ng/ml) inhibited K+-evoked [3H]GABA release from hippocampal synaptosomes. This action was also mediated by phosphorylation of the TrkB receptor, but was independent of Ca2+ entry into synaptosomes through voltage-sensitive calcium channels. Blockade of transport of GABA with SKF 89976a (20 μM) prevented the inhibitory action of BDNF upon GABA release, indicating that BDNF influences the activity of GABA transporters. It is concluded that BDNF influences in an opposite way, through distinct mechanisms, the release of glutamate and the release of GABA from hippocampal synaptosomes.