Greenamyre J T, Porter R H
Department of Neurology, University of Rochester (New York) Medical Center 14642-8673.
Neurology. 1994 Nov;44(11 Suppl 8):S7-13.
Glutamate is the predominant excitatory neurotransmitter in the mammalian CNS. The neurotransmitter pool of glutamate is stored in synaptic vesicles and, upon depolarization, is released into the synaptic cleft in a Ca(2+)-dependent fashion. Glutamate is cleared from the synaptic cleft by high-affinity, Na(+)-dependent uptake carriers located in both neurons and glia. Glutamate acts on several distinct families of receptors, each of which has multiple subtypes with distinct pharmacologic and physiologic properties. Under some conditions, glutamate and related compounds act as excitotoxins and might participate in the events leading to neuronal damage and death in a variety of acute and chronic neurologic disorders. The potential for glutamate to become an excitotoxin is highly dependent upon neuronal metabolic status. A great deal of interest in developing selective, well-tolerated glutamate receptor antagonists for the treatment of a variety of neurologic disorders exists.
谷氨酸是哺乳动物中枢神经系统中主要的兴奋性神经递质。谷氨酸的神经递质池储存在突触小泡中，在去极化时，以钙离子依赖的方式释放到突触间隙。谷氨酸通过位于神经元和神经胶质细胞中的高亲和力、钠离子依赖的摄取载体从突触间隙清除。谷氨酸作用于几个不同的受体家族，每个家族都有多个具有不同药理和生理特性的亚型。在某些情况下，谷氨酸及相关化合物可作为兴奋性毒素，并可能参与导致多种急性和慢性神经系统疾病中神经元损伤和死亡的事件。谷氨酸成为兴奋性毒素的可能性高度依赖于神经元的代谢状态。人们对开发用于治疗多种神经系统疾病的选择性、耐受性良好的谷氨酸受体拮抗剂有着浓厚的兴趣。
