title: Protein kinase A mediates adenosine A2a receptor modulation of neurotransmitter release via synapsin I phosphorylation in cultured cells from medulla oblongata.
abstract: Synaptic transmission is an essential process for neuron physiology. Such process is enabled in part due to modulation of neurotransmitter release. Adenosine is a synaptic modulator of neurotransmitter release in the Central Nervous System, including neurons of medulla oblongata, where several nuclei are involved with neurovegetative reflexes. Adenosine modulates different neurotransmitter systems in medulla oblongata, specially glutamate and noradrenaline in the nucleus tractussolitarii, which are involved in hypotensive responses. However, the intracellular mechanisms involved in this modulation remain unknown. The adenosine A2a receptor modulates neurotransmitter release by activating two cAMP protein effectors, the protein kinase A and the exchange protein activated by cAMP. Therefore, an in vitro approach (cultured cells) was carried out to evaluate modulation of neurotransmission by adenosine A2a receptor and the signaling intracellular pathway involved. Results show that the adenosine A2a receptor agonist, CGS 21680, increases neurotransmitter release, in particular, glutamate and noradrenaline and such response is mediated by protein kinase A activation, which in turn increased synapsin I phosphorylation. This suggests a mechanism of A2aR modulation of neurotransmitter release in cultured cells from medulla oblongata of Wistar rats and suggest that protein kinase A mediates this modulation of neurotransmitter release via synapsin I phosphorylation.
authors.affiliation: Department of Physiology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Joao Paulo Pontes
authors.initials: JP
authors.lastname: Matsumoto
authors.affiliation: Department of Physiology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Marina Gomes
authors.initials: MG
authors.lastname: Almeida
authors.affiliation: Department of Physiology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Emerson Augusto
authors.initials: EA
authors.lastname: Castilho-Martins
authors.affiliation: Department of Physiology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Maisa Aparecida
authors.initials: MA
authors.lastname: Costa
authors.affiliation: Department of Physiology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: drfchadi@usp.br.
authors.forename: Debora Rejane
authors.initials: DR
authors.lastname: Fior-Chadi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D008526:Medulla Oblongata / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D043705:Receptor, Adenosine A2A; D016704:Synapsins; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Adenosine A(2a) receptor; Cell culture; Medulla oblongata; Neuromodulation; Protein kinase A; Synapsin