Presynaptic signalling mediated by mono- and dinucleotides in the central nervous system

M.Teresa Miras-Portugal, Miguel Dı́az-Hernández, Rosa Gomez-Villafuerte, Javier Gualix, Enrique Castro, Jesús Pintor
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引用次数: 10

Abstract

Synaptosomal preparations from rat midbrain exhibit specific responses to both ATP and Ap5A, which elicit a Ca2+ entrance to the presynaptic terminals. Studies of isolated single terminals showed that not all the terminals contain ionotropic receptors for nucleotides, in fact only 46% of them do. Of these, 12% responded only to the dinucleotide Ap5A, and 20% to the mononucleotide ATP. At the presynaptic level, diinosine pentaphosphate, Ip5I, is a good tool to specifically block dinucleotide responses, which are inhibited at low nM concentration, versus the high μM concentrations required to block ATP responses. There is evidence for a presynaptic control of mononucleotide and dinucleotide responses, mediated by metabotropic and ionotropic receptors. Stimulation of adenosine A1 receptors increases the affinity of dinucleotide receptors by five orders of magnitude, from 30 μM to 680 pM for control and in the presence of A1 agonist, respectively.

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中枢神经系统单核苷酸和二核苷酸介导的突触前信号传导
来自大鼠中脑的突触体制剂对ATP和Ap5A均表现出特异性反应,从而引发Ca2+进入突触前末端。对分离的单个末端的研究表明,并非所有的末端都含有核苷酸的离子化受体,事实上只有46%的末端含有。其中,12%只对二核苷酸Ap5A有反应,20%对单核苷酸ATP有反应。在突触前水平,五磷酸二肌苷(Ip5I)是特异性阻断二核苷酸反应的好工具,二核苷酸反应在低nM浓度下被抑制,而高μM浓度则需要阻断ATP反应。有证据表明突触前控制单核苷酸和二核苷酸反应,由代谢和嗜离子受体介导。刺激腺苷A1受体可使二核苷酸受体的亲和力增加5个数量级,分别从30 μM到680 pM(对照)和A1激动剂存在时。
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