Orrego F, Villanueva S
Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
Neuroscience. 1993 Oct;56(3):539-55. doi: 10.1016/0306-4522(93)90355-j.
The chemical nature of the central transmitter responsible for fast excitatory events and other related phenomena is analysed against the historical background that has progressively clarified the structure and function of central synapses. One of the problems posed by research in this field has been whether one or more of the numerous excitatory substances endogenous to the brain is responsible for fast excitatory synaptic transmission, or if such a substance is, or was, a previously unknown one. The second question is related to the presence in the CNS of three main receptor types related to fast excitatory transmission, the so-called alpha-amino-3-hydroxy-5-methylisoxazole propionic acid, kainate and N-methyl-D-aspartate receptors. This implies the possibility that each receptor type might have its own endogenous agonist, as has sometimes been suggested. To answer such questions, an analysis was done of how different endogenous substances, including L-glutamate, L-aspartate, L-cysteate, L-homocysteate, L-cysteine sulfinate, L-homocysteine sulfinate, N-acetyl-L-aspartyl glutamate, quinolinate, L-sulfoserine, S-sulfo-L-cysteine, as well as possible unknown compounds, were able to fulfil the more important criteria for transmitter identification, namely identity of action, induced release, and presence in synaptic vesicles. The conclusion of this analysis is that glutamate is clearly the main central excitatory transmitter, because it acts on all three of the excitatory receptors, it is released by exocytosis and, above all, it is present in synaptic vesicles in a very high concentration, comparable to the estimated number of acetylcholine molecules in a quantum, i.e. 6000 molecules. Regarding a possible transmitter role for aspartate, for which a large body of evidence has been presented, it seems, when this evidence is carefully scrutinized, that it is either inconclusive, or else negative. This suggests that aspartate is not a classical central excitatory transmitter. From this analysis, it is suggested that the terms alpha-amino-3-hydroxy-5-methylisoxazole propionic acid, kainate and N-methyl-D-aspartate receptors, should be changed to that of glutamate receptors, and, more specifically, to GLUA, GLUK and GLUN receptors, respectively. When subtypes are described, a Roman numeral may be added, as in GLUNI, GLUNII, and so on.
在逐步阐明中枢突触结构和功能的历史背景下，分析了负责快速兴奋性事件及其他相关现象的中枢递质的化学性质。该领域研究提出的问题之一是，大脑中众多内源性兴奋性物质中的一种或多种是否负责快速兴奋性突触传递，或者这种物质是否是一种先前未知的物质。第二个问题与中枢神经系统中与快速兴奋性传递相关的三种主要受体类型的存在有关，即所谓的α-氨基-3-羟基-5-甲基异恶唑丙酸、海人酸和N-甲基-D-天冬氨酸受体。这意味着每种受体类型可能有其自身内源性激动剂的可能性，正如有时有人所建议的那样。为了回答这些问题，分析了不同的内源性物质，包括L-谷氨酸、L-天冬氨酸、L-半胱氨酸、L-高半胱氨酸、L-半胱氨酸亚磺酸盐、L-高半胱氨酸亚磺酸盐、N-乙酰-L-天冬氨酰谷氨酸、喹啉酸、L-磺丝氨酸、S-磺基-L-半胱氨酸以及可能的未知化合物，如何能够满足递质鉴定的更重要标准，即作用相同、诱导释放以及存在于突触小泡中。该分析的结论是，谷氨酸显然是主要的中枢兴奋性递质，因为它作用于所有三种兴奋性受体，通过胞吐作用释放，最重要的是，它以非常高的浓度存在于突触小泡中，这一浓度与一个量子中估计的乙酰胆碱分子数量相当，即6000个分子。关于天冬氨酸可能的递质作用，虽然已经提出了大量证据，但仔细审查这些证据时，似乎要么没有定论，要么是否定的。这表明天冬氨酸不是经典的中枢兴奋性递质。从该分析中建议，α-氨基-3-羟基-5-甲基异恶唑丙酸、海人酸和N-甲基-D-天冬氨酸受体这几个术语应分别改为谷氨酸受体，更具体地说，分别改为GLUA、GLUK和GLUN受体。当描述亚型时，可以添加罗马数字，如GLUNI、GLUNII等。
