Pousinha, Paula A.Diógenes, Maria JoséRibeiro, Joaquim A.Sebastião, Ana M2013-04-032013-04-032006Neuroscience Letters 404 (2006) 143–1470304-3940http://dx.doi.org/10.1016/j.neulet.2006.05.036http://hdl.handle.net/10451/8189© 2006 ElsevierMotor 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.engAdenosineAdenosine A2A receptorBrain-derived neurotrophic factor (BDNF)TrkB receptorNeuromuscular junctionNeuromuscular transmissionjournal article