Matsumoto Joao Paulo Pontes, Almeida Marina Gomes, Castilho-Martins Emerson Augusto, Costa Maisa Aparecida, Fior-Chadi Debora Rejane
Department of Physiology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.
Department of Physiology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.
Neurosci Res. 2014 Aug;85:1-11. doi: 10.1016/j.neures.2014.05.007. Epub 2014 Jun 6.
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.
突触传递是神经元生理学的一个基本过程。该过程部分是由于神经递质释放的调节而得以实现。腺苷是中枢神经系统中神经递质释放的一种突触调节剂，包括延髓的神经元，其中几个核参与神经植物性反射。腺苷调节延髓中的不同神经递质系统，特别是孤束核中的谷氨酸和去甲肾上腺素，它们参与降压反应。然而，这种调节所涉及的细胞内机制仍然未知。腺苷A2a受体通过激活两种环磷酸腺苷（cAMP）蛋白效应器，即蛋白激酶A和由cAMP激活的交换蛋白，来调节神经递质的释放。因此，采用了一种体外方法（培养细胞）来评估腺苷A2a受体对神经传递的调节以及所涉及的细胞内信号通路。结果表明，腺苷A2a受体激动剂CGS 21680增加神经递质的释放，特别是谷氨酸和去甲肾上腺素，并且这种反应是由蛋白激酶A的激活介导的，蛋白激酶A的激活进而增加了突触素I的磷酸化。这提示了Wistar大鼠延髓培养细胞中A2aR调节神经递质释放的一种机制，并表明蛋白激酶A通过突触素I磷酸化介导这种神经递质释放的调节。
