title: Activation of adenosine A2A receptor facilitates brain-derived neurotrophic factor modulation of synaptic transmission in hippocampal slices.
abstract: Both brain-derived neurotrophic factor (BDNF) and adenosine influence neuronal plasticity. We now investigated how adenosine influences the action of BDNF on synaptic transmission in the CA1 area of the rat hippocampal slices. Alone, BDNF (20-100 ng/ml) did not significantly affect field EPSPs (fEPSPs). However, a 2 min pulse of high-K(+) (10 mm) 46 min before the application of BDNF (20 ng/ml) triggered an excitatory action, an effect blocked by the TrkB receptor inhibitor K252a (200 nm), by the adenosine A(2A) receptor antagonist ZM 241385 (50 nm), and by the protein kinase A inhibitor H-89 (1 microm). Presynaptic, rather than postsynaptic depolarization was required to trigger the BDNF action because after K(+) depolarization BDNF also increased EPSCs recorded from pyramidal neurons voltage-clamped at -60 mV, and transient postsynaptic depolarization was unable to unmask the BDNF action. A weak theta burst stimulation of the afferents could elicit potentiation of synaptic transmission only when applied in the presence of BDNF. Activation of adenosine A(2A) receptors with CGS 21680 (10 nm), or the increase in extracellular adenosine levels induced by 5-iodotubercidin (100 nm) triggered the excitatory action of BDNF, a process prevented by ZM 241385 and by H-89. In the presence of dibutyryl-cAMP (0.5 mm), BDNF also increased fEPSPs but postsynaptic cAMP (0.5 mm) was unable to trigger the BDNF action. It is concluded that presynaptic activity-dependent release of adenosine, through activation of A(2A) receptors, facilitates BDNF modulation of synaptic transmission at hippocampal synapses.
authors.affiliation: Laboratory of Neurosciences and Institute of Pharmacology, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Diógenes
authors.forename: Catarina Cunha
authors.initials: CC
authors.lastname: Fernandes
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Sebastião
authors.forename: Joaquim Alexandre
authors.initials: JA
authors.lastname: Ribeiro
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism*; D020813:Receptor, trkB / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D003994:Bucladesine; C049985:staurosporine aglycone; D000248:Adenosine Kinase; D020813:Receptor, trkB; D000241:Adenosine; D011188:Potassium