Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.
School of Clinical Sciences, University of Bristol, Bristol, UK.
Neurochem Res. 2019 Mar;44(3):516-530. doi: 10.1007/s11064-018-2640-6. Epub 2018 Oct 4.
In the 1960s and 70s, biochemical and pharmacological evidence was pointing toward glutamate as a synaptic transmitter at a number of distinct receptor classes, known as NMDA and non-NMDA receptors. The field, however, lacked a potent and highly selective antagonist to block these putative postsynaptic receptors. So, the discoveries in the early 1980s of D-AP5 as a selective NMDA receptor antagonist and of its ability to block synaptic events and plasticity were a major breakthrough leading to an explosion of knowledge about this receptor subtype. During the next 10 years, the role of NMDA receptors was established in synaptic transmission, long-term potentiation, learning and memory, epilepsy, pain, among others. Hints at pharmacological heterogeneity among NMDA receptors were followed by the cloning of separate subunits. The purpose of this review is to recognize the important contributions made in the 1980s by Graham L. Collingridge and other key scientists to the advances in our understanding of the functions of NMDA receptors throughout the central nervous system.
在 20 世纪 60 年代和 70 年代，生化和药理学证据表明谷氨酸是多种不同受体类型（称为 NMDA 和非 NMDA 受体）的突触递质。然而，该领域缺乏一种有效的、高度选择性的拮抗剂来阻断这些假定的突触后受体。因此，20 世纪 80 年代早期发现 D-AP5 作为选择性 NMDA 受体拮抗剂及其阻断突触事件和可塑性的能力是一个重大突破，导致了对这种受体亚型的知识爆炸。在接下来的 10 年中，NMDA 受体在突触传递、长时程增强、学习和记忆、癫痫、疼痛等方面的作用得到了确立。NMDA 受体的药理学异质性的提示随后是单独亚基的克隆。本综述的目的是认识 Graham L. Collingridge 和其他关键科学家在 20 世纪 80 年代对我们理解 NMDA 受体在中枢神经系统中的功能的进展所做出的重要贡献。
Zotero 插件
