Modulation of Glutamate Receptors: Molecular Mechanisms and Functional Implications

Abstract

The concept that excitatory amino acids (EAA) function as neurotransmitters mediating neuronal excitation is now well established . Their receptors are among the most abundant in the mammalian central nervous system. Recent progress in the understanding of EAA receptors has been summarized in several review articles that focus on the selectivity of agonists and competitive antagonists for the particular subclasses of EAA receptors ( 1 -4) , noncompeti­ tive EAA receptor antagonists (5) , anatomical organization of EAA receptors in the eNS (6) , characteristics of ionic channels associated with EAA recep­ tors (7 , 8) and the role of EAA receptors in synaptic plasticity (9) , long-term potentiation ( 1 0) , and neurotoxicity ( 1 1 ) . The current classification of EAA receptors, originating mostly from iontophoretic and radioligand-binding studies, is based on ligand selectivity in distinguishing receptors for N-methyl-D-aspartate (NMDA), kainate, quis­ qualate, and 2-amino-4-phosphonobutyrate (APB) (3). Among endogenous compounds, L-glutamate seems to activate all of the above receptors, although other compounds found in the brain tissue, such as L-aspartate, L­ homocysteate or N-acetyl-aspartylglutamate, may activate particular EAA receptor subtypes (3) . Although the activity of glutamate receptors may be regulated by mech­ anisms controlling the release and reuptake of the transmitter ( 1 2) , an increas-