http://hdl.handle.net/10451/4349 2013-06-19T19:20:41Z 2013-06-19T19:20:41Z Cunha-Reis, D. Fontinha, B. M. Ribeiro, J. A. Sebastião, A. M. http://hdl.handle.net/10451/8275 2013-04-12T15:15:21Z 2007-01-01T00:00:00Z

Title: Tonic adenosine A1 and A2A receptor activation is required for the excitatory action of VIP on synaptic transmission in the CA1 area of the hippocampus Authors: Cunha-Reis, D.; Fontinha, B. M.; Ribeiro, J. A.; Sebastião, A. M. Abstract: Adenosine can regulate synaptic transmission through modulation of the action of other neurotransmitters. The influence of adenosine on VIP enhancement of synaptic transmission in hippocampal slices was investigated. Facilitation of fEPSP slope by 1 nM VIP (23.3 ± 1.3%) was turned into an inhibition (-12.1 ± 3.4%) when extracellular endogenous adenosine was removed using adenosine deaminase (ADA, 1 U/ml). Blockade of adenosine A1 receptors with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nM) or of A2A receptors with ZM241385 (20 nM) attenuated the effect of VIP. When both DPCPX and ZM241385 were present the effect of VIP was abolished. In the presence of ADA, selective A1 receptor activation with N6-cyclopentyladenosine (CPA, 15 nM) or A2A receptor-activation with CGS21680 (10 nM) partially readmitted the excitatory effect of VIP on fEPSPs. In contrast, facilitation of PS amplitude by 1 nM VIP (19.1 ± 1.2%) was attenuated in the presence of ADA or DPCPX but was not changed by ZM241385. CPA, in the presence of ADA, fully restored the effect of VIP on PS amplitude. In conclusion, VIP facilitation of synaptic transmission to hippocampal pyramidal cell dendrites is dependent on both A1 and A2A receptor activation by endogenous adenosine. VIP effects on PS amplitude are only dependent on A1 adenosine receptor activation. This differential sensitivity to adenosine modulation might be due to the different VIP circuits contributing to VIP effects on pyramidal cell dendrites and pyramidal cell bodies.In contrast, facilitation of PS amplitude by 1 nM VIP (19.1 1.2%) was attenuated in the presence of ADA or DPCPX but was not changed by ZM241385. CPA, in the presence of ADA, fully restored the effect of VIP on PS amplitude. In conclusion, VIP facilitation of synaptic transmission to hippocampal pyramidal cell dendrites is dependent on both A1 and A2A receptor activation by endogenous adenosine. VIP effects on PS amplitude are only dependent on A1 adenosine receptor activation. This differential sensitivity to adenosine modulation might be due to the different VIP circuits contributing to VIP effects on pyramidal cell dendrites and pyramidal cell bodies. 1.2%) was attenuated in the presence of ADA or DPCPX but was not changed by ZM241385. CPA, in the presence of ADA, fully restored the effect of VIP on PS amplitude. In conclusion, VIP facilitation of synaptic transmission to hippocampal pyramidal cell dendrites is dependent on both A1 and A2A receptor activation by endogenous adenosine. VIP effects on PS amplitude are only dependent on A1 adenosine receptor activation. This differential sensitivity to adenosine modulation might be due to the different VIP circuits contributing to VIP effects on pyramidal cell dendrites and pyramidal cell bodies. Description: © 2006 Elsevier Ltd

2007-01-01T00:00:00Z Pousinha, Paula A. Diogenes, Maria José Ribeiro, Joaquim Alexandre Sebastião, Ana M. http://hdl.handle.net/10451/8189 2013-04-03T11:20:14Z 2006-01-01T00:00:00Z

Title: Triggering of BDNF facilitatory action on neuromuscular transmission by adenosine A2A receptors Authors: Pousinha, Paula A.; Diogenes, Maria José; Ribeiro, Joaquim Alexandre; Sebastião, Ana M. Abstract: Motor nerve terminals possess adenosine A2A receptors and brain derived neurotrophic factor (BDNF) TrkB receptors. In the present work we evaluated how BDNF actions on neuromuscular transmission would be influenced by adenosine A2A receptors activation. BDNF (20–100 ng/ml)on its own was devoid of effect on evoked endplate potentials (EPPs) recorded intracellularly from rat innervated diaphragms paralysed with tubocurarine. However, when BDNF was applied 45 min after a brief (2 min) depolarizing KCl (10 mM) pulse or when the adenosine A2A receptors were activated with CGS 21680 (10 nM), BDNF (20 ng/ml) increased EPPs amplitude without influencing the resting membrane potential of the muscle fibre. The action of BDNF was prevented by the adenosine A2A receptor antagonist, ZM 241385 (50 nM) as well as by the TrkB receptor phosphorylation inhibitor, K252a (200 nM). The PKA inhibitor, H-89 (1 μM), prevented the excitatory effect of CGS 21680 (10 nM) on EPPs as well as prevented its ability to trigger a BDNF effect. The PLCγ inhibitor, U73122 (5 μM), did not prevent the excitatory action of CGS 21680 (10 nM) on neuromuscular transmission, but abolished the action of BDNF in the presence of the A2A receptor agonist. The results suggest the following sequence of events in what concerns cooperativity between A2A receptors and TrkB receptors at the neuromuscular junction: A2A receptor activates the PKA pathway, which promotes the action of BDNF through TrkB receptors coupled to PLCγ, leading to enhancement of neuromuscular transmission. Description: © 2006 Elsevier

2006-01-01T00:00:00Z Quiroz, César Gomes, Catarina Pak, Arlene C. Ribeiro, Joaquim A. Goldberg, Steven R. Hope, Bruce T. Ferré, Sergi http://hdl.handle.net/10451/8188 2013-04-03T10:36:12Z 2006-10-18T00:00:00Z

Title: Blockade of adenosine A2A receptors prevents protein phosphorylation in the striatum induced by cortical stimulation Authors: Quiroz, César; Gomes, Catarina; Pak, Arlene C.; Ribeiro, Joaquim A.; Goldberg, Steven R.; Hope, Bruce T.; Ferré, Sergi Abstract: Previous studies have shown that cortical stimulation selectively activates extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and immediate early gene expression in striatal GABAergic enkephalinergic neurons. In the present study, we demonstrate that blockade of adenosine A2A receptors with caffeine or a selective A2A receptor antagonist counteracts the striatal activation of cAMP– protein kinase A cascade (phosphorylation of the Ser845 residue of the glutamate receptor 1 subunit of the AMPA receptor) and mitogenactivated protein kinase (ERK1/2 phosphorylation) induced by the in vivo stimulation of corticostriatal afferents. The results indicate that A2A receptors strongly modulate the efficacy of glutamatergic synapses on striatal enkephalinergic neurons. Description: ©2006 Society for Neuroscience

2006-10-18T00:00:00Z Gomes, Catarina A. R. V. Vaz, Sandra H. Ribeiro, Joaquim A. Sebastião, Ana M. http://hdl.handle.net/10451/8093 2013-03-26T14:14:10Z 2006-01-01T00:00:00Z

Title: Glial cell line-derived neurotrophic factor (GDNF) enhances dopamine release from striatal nerve endings in an adenosine A2A receptor-dependent manner Authors: Gomes, Catarina A. R. V.; Vaz, Sandra H.; Ribeiro, Joaquim A.; Sebastião, Ana M. Abstract: Both glial cell line-derived neurotrophic factor (GDNF) and adenosine influence dopaminergic function in the striatum. We now evaluated the GDNF effect on dopamine release from rat striatal nerve endings and if this effect of GDNF is modulated by adenosine A2A receptors.Dopamine release was evoked twice (S1 and S2); GDNF was added before S2 and drugs used to modify GDNF actions were present during both stimulation periods. The effect of GDNF was taken as the change in the S2/S1 ratio in the absence and in the presence of GDNF in the same experimental conditions. GDNF (3–30 ng/ml) increased dopamine release from K+ (20 mM, 2 min) stimulated synaptosomes and electrically (2 Hz, 2 min) stimulated striatal slices, an effect dependent upon tonic adenosine A2A receptor activation, since it was blocked by the A2A receptor antagonist, SCH 58261 (50 nM). Activation of A2A receptors with CGS 21680 (10 nM) potentiated the effect of GDNF in synaptosomes. CGS 21680 also potentiated the effect of GDNF in striatal slices, providing that GABAergic transmission was inhibited; if not, the action of GDNF was attenuated by CGS 21680. Blockade of GABAergic transmission per se increased dopamine release, but attenuated the effect of GDNF upon dopamine release in slices.The results suggest that GDNF enhances dopamine release by acting presynaptically at the striatum, an action that requires adenosine A2A receptor activity. Furthermore, in striatal slices, the action of GDNF as well as its modulation by adenosine A2A receptor activation appears to be also under control of GABAergic transmission. Description: © 2006 Elsevier B.V. All rights reserved

2006-01-01T00:00:00Z