D-Aspartic acid is a novel endogenous neurotransmitter
D-Aspartic acid is a novel endogenous neurotransmitter
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DOI：
10.1096/fj.10-168492
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发表时间：
2011-03-01
期刊：
影响因子：
4.8
通讯作者：
D'Aniello, Antimo
中科院分区：
文献类型：
--
作者：
D'Aniello, Salvatore;Somorjai, Ildiko;D'Aniello, Antimo
D-天冬氨酸（D-Asp）存在于无脊椎动物和脊椎动物的神经内分泌组织中，在那里它执行重要的生理功能并参与神经系统发育。我们在这里表明，D-天冬氨酸是一种新的内源性神经递质在两个远亲动物，哺乳动物（褐家鼠）和软体动物（Loligo vulgaris）。我们的主要研究结果表明，D-Asp在轴突终末的突触囊泡中浓度很高，在神经元中通过D-天冬氨酸消旋酶将L-Asp转化为D-Asp来合成这种氨基酸，K+去极化神经末梢引起D-Asp以Ca~（2+）依赖的方式立即释放; D-Asp的特异性受体存在于突触后膜，如结合试验和鱿鱼皮肤色素细胞的扩张所证明的; D-天冬氨酸氧化酶是氧化D-Asp的特异性酶，存在于突触后膜中;用D-Asp刺激神经末梢通过增加第二信使cAMP触发信号转导。综上所述，这些数据表明，D-Asp满足被认为是一种新型内源性神经递质所需的所有标准。鉴于其在神经发生，学习和神经病理学中的已知作用，我们的研究结果对生物医学和临床研究具有重要意义。D'Aniello，S.，索莫尔贾伊岛Garcia-Fernandez，J.，Topo，E.，D'Aniello，A. D-天冬氨酸是一种新的内源性神经递质。FASEB J.25，1014 - 1027（2011）。www.fasebj.org
D-Aspartic acid (D-Asp) is present in invertebrate and vertebrate neuroendocrine tissues, where it carries out important physiological functions and is implicated in nervous system development. We show here that D-Asp is a novel endogenous neurotransmitter in two distantly related animals, a mammal (Rattus norvegicus) and a mollusk (Loligo vulgaris). Our main findings demonstrate that D-Asp is present in high concentrations in the synaptic vesicles of axon terminals; synthesis for this amino acid occurs in neurons by conversion of L-Asp to D-Asp via D-aspartate racemase; depolarization of nerve endings with K+ ions evokes an immediate release of D-Asp in a Ca2+ dependent manner; specific receptors for D-Asp occur at the postsynaptic membrane, as demonstrated by binding assays and by the expansion of squid skin chromatophores; D-aspartate oxidase, the specific enzyme that oxidizes D-Asp, is present in the postsynaptic membranes; and stimulation of nerve endings with D-Asp triggers signal transduction by increasing the second messenger cAMP. Taken together, these data demonstrate that D-Asp fulfills all criteria necessary to be considered a novel endogenous neurotransmitter. Given its known role in neurogenesis, learning, and neuropathologies, our results have important implications for biomedical and clinical research.-D'Aniello, S., Somorjai, I., Garcia-Fernandez, J., Topo, E., D'Aniello, A. D-Aspartic acid is a novel endogenous neurotransmitter. FASEB J. 25, 1014-1027 (2011). www.fasebj.org