Glutamic Acid and Aspartic Acid

These two excitatory amino acids (EAAs) are widely distributed throughout the mammalian CNS. Their administration leads to rapid depolarization of neurons and an increase in firing rate. There are two distinct classes of EAA receptors: ionotropic receptors and metabotropic receptors. The ionotropic receptors directly gate ion channels, while the metabotropic receptors are coupled to intracellular G proteins. Receptors are named according to their sensitivity to the action of selective agonists (Table 24.1). The best-characterized receptor is known as the NMDA (N-methyl-d-aspartate) receptor, which directly gates a Mg++ cation channel that is also permeable to Ca++ and Na+. Compounds that block the NMDA receptor complex may attenuate the neuronal damage following anoxia, such as occurs during a stroke; much of the neuronal damage associated with strokes may be related to the release of glutamic acid, aspartic acid, or both. Similarly, neuronal damage may occur as a result of seizures, and this also may be related to excessive EAA release. Antagonists of the NMDA receptor complex are being studied for possible uses in strokes and other types of hypoxia.

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