Neurochemistry of L-glutamate transport in the CNS: A review of thirty years of progress

The review highlights the landmark studies leading from the discovery and i nitial characterization of the Na+-dependent "high affinity" uptake in the mammalian brain to the cloning of individual transporters and the subsequen t expansion of the field into the realm of molecular biology. When the data and hypotheses from 1970's are confronted with the recent developments in the field, we can conclude that the suggestions made nearly thirty years ag o were essentially correct: the uptake, mediated by an active transport int o neurons and glial cells, serves to control the extracellular concentratio ns Of L-glutamate and prevents the neurotoxicity. The modern techniques of molecular biology may have provided additional data on the nature and locat ion of the transporters but the classical neurochemical approach, using str uctural analogues of glutamate designed as specific inhibitors or substrate s for glutamate transport, has been crucial for the investigations of parti cular roles that glutamate transport might play in health and disease. Anal ysis of recent structure/activity data presented in this review has yielded a novel insight into the pharmacological characteristics Of L-glutamate tr ansport, suggesting existence of additional heterogeneity in the system, be yond that so far discovered by molecular genetics. More compounds that spec ifically interact with individual glutamate transporters are urgently neede d for more detailed investigations of neurochemical characteristics of glut amatergic transport and its integration into the glutamatergic synapses in the central nervous system. A review with 162 references.